Pub Date : 2024-10-04eCollection Date: 2024-01-01DOI: 10.1177/17588359241284911
Al Jarroudi Ouissam, Chibani Hind, Brahmi Sami Aziz, Afqir Said
Pancreatic cancer (PC) is an aggressive disease that is challenging to treat and is associated with a high mortality rate. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), and the existing treatment options are insufficient for PDAC patients. Due to the complexity and heterogeneity of PDAC, personalized medicine is necessary for effectively treating this illness. To achieve this, it is essential to understand the mechanism of PDAC carcinogenesis. Targeted therapies are a promising strategy to improve patient outcomes. Aberrant activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a crucial role in PC pathogenesis, from initiation to progression. This review provides a comprehensive overview of the current state of knowledge regarding the PI3K pathway in PDAC, summarizes clinical data on PI3K pathway inhibition in PDAC, and explores potential effective combinations that are a promising direction requiring further investigation in PDAC.
{"title":"Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?","authors":"Al Jarroudi Ouissam, Chibani Hind, Brahmi Sami Aziz, Afqir Said","doi":"10.1177/17588359241284911","DOIUrl":"https://doi.org/10.1177/17588359241284911","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is an aggressive disease that is challenging to treat and is associated with a high mortality rate. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), and the existing treatment options are insufficient for PDAC patients. Due to the complexity and heterogeneity of PDAC, personalized medicine is necessary for effectively treating this illness. To achieve this, it is essential to understand the mechanism of PDAC carcinogenesis. Targeted therapies are a promising strategy to improve patient outcomes. Aberrant activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a crucial role in PC pathogenesis, from initiation to progression. This review provides a comprehensive overview of the current state of knowledge regarding the PI3K pathway in PDAC, summarizes clinical data on PI3K pathway inhibition in PDAC, and explores potential effective combinations that are a promising direction requiring further investigation in PDAC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241284911"},"PeriodicalIF":4.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04eCollection Date: 2024-01-01DOI: 10.1177/17588359241284929
Yunchang Meng, Qingfeng Zhang, Ranpu Wu, Huijuan Li, Zhaofeng Wang, Yang Yao, Xinjing Li, Zhangxuan Chen, Yanzhuo Gong, Hongbing Liu
Background: Neoadjuvant (NE), adjuvant (AD), and perioperative (PE) immunotherapies have gained validation in early-stage non-small cell lung cancer (NSCLC) trials. However, a comprehensive assessment of their comparative efficacy and safety is lacking.
Objectives: To compare the efficacy and safety of NE, AD, and PE immunotherapies in early-stage NSCLC.
Design: A systematic review and network meta-analysis using a Bayesian framework.
Data sources and methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) of immune checkpoint inhibitors plus chemotherapy (CT) for early-stage NSCLC. Hazard ratios (HRs) and odds ratios (ORs) for binary endpoints with 95% confidence intervals (CIs) were calculated.
Results: We included 10 RCTs involving 5569 NSCLC patients, categorized as NE, PE, or AD immunotherapy. Indirect comparisons highlighted differences in efficacy between PE and AD immunotherapy, specifically in event-free survival (EFS)/disease-free survival (DFS) (HR = 0.72, 95% CI: 0.53-0.96). NE/PE immunotherapies improved pathologic complete response (pCR) (OR = 7.56, 95% CI: 5.24-10.92), major pathologic response (MPR) (OR = 5.46, 95% CI: 3.97-7.51), and EFS (HR = 0.58, 95% CI: 0.52-0.65), while AD immunotherapy enhanced DFS (HR = 0.78, 95% CI: 0.69-0.90). Overall survival (OS) benefits were seen only with PE immunotherapy (HR = 0.66, 95% CI: 0.55-0.81). PE treatment improved EFS across various subgroups (PD-L1 < 1%, IIIB, squamous, female, without MPR/pCR, epidermal growth factor receptor (EGFR) mutant-negative), except EGFR mutant-positive NSCLC (HR = 0.54, 95% CI: 0.21-1.43). AD (OR = 1.81, 95% CI: 1.20-2.73) and PE (OR = 1.28, 95% CI: 1.10-1.50) immunotherapies were associated with higher grade ⩾3 adverse events.
Conclusion: In the three treatment modalities, PE immunotherapy appears to be more effective than AD immunotherapy, with PE showing significant advantages in certain subgroups that NE does not. NE and PE immunotherapy significantly improved pCR, MPR, and EFS, while AD immunotherapy significantly improved DFS in NSCLC patients compared to the control group. However, only PE immunotherapy significantly improved OS. Differences in efficacy between NE and PE across the entire population of resectable NSCLC remain to be explored in additional studies.
{"title":"Efficacy and safety of perioperative, neoadjuvant, or adjuvant immunotherapy alone or in combination with chemotherapy in early-stage non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials.","authors":"Yunchang Meng, Qingfeng Zhang, Ranpu Wu, Huijuan Li, Zhaofeng Wang, Yang Yao, Xinjing Li, Zhangxuan Chen, Yanzhuo Gong, Hongbing Liu","doi":"10.1177/17588359241284929","DOIUrl":"https://doi.org/10.1177/17588359241284929","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant (NE), adjuvant (AD), and perioperative (PE) immunotherapies have gained validation in early-stage non-small cell lung cancer (NSCLC) trials. However, a comprehensive assessment of their comparative efficacy and safety is lacking.</p><p><strong>Objectives: </strong>To compare the efficacy and safety of NE, AD, and PE immunotherapies in early-stage NSCLC.</p><p><strong>Design: </strong>A systematic review and network meta-analysis using a Bayesian framework.</p><p><strong>Data sources and methods: </strong>We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) of immune checkpoint inhibitors plus chemotherapy (CT) for early-stage NSCLC. Hazard ratios (HRs) and odds ratios (ORs) for binary endpoints with 95% confidence intervals (CIs) were calculated.</p><p><strong>Results: </strong>We included 10 RCTs involving 5569 NSCLC patients, categorized as NE, PE, or AD immunotherapy. Indirect comparisons highlighted differences in efficacy between PE and AD immunotherapy, specifically in event-free survival (EFS)/disease-free survival (DFS) (HR = 0.72, 95% CI: 0.53-0.96). NE/PE immunotherapies improved pathologic complete response (pCR) (OR = 7.56, 95% CI: 5.24-10.92), major pathologic response (MPR) (OR = 5.46, 95% CI: 3.97-7.51), and EFS (HR = 0.58, 95% CI: 0.52-0.65), while AD immunotherapy enhanced DFS (HR = 0.78, 95% CI: 0.69-0.90). Overall survival (OS) benefits were seen only with PE immunotherapy (HR = 0.66, 95% CI: 0.55-0.81). PE treatment improved EFS across various subgroups (PD-L1 < 1%, IIIB, squamous, female, without MPR/pCR, epidermal growth factor receptor (EGFR) mutant-negative), except EGFR mutant-positive NSCLC (HR = 0.54, 95% CI: 0.21-1.43). AD (OR = 1.81, 95% CI: 1.20-2.73) and PE (OR = 1.28, 95% CI: 1.10-1.50) immunotherapies were associated with higher grade ⩾3 adverse events.</p><p><strong>Conclusion: </strong>In the three treatment modalities, PE immunotherapy appears to be more effective than AD immunotherapy, with PE showing significant advantages in certain subgroups that NE does not. NE and PE immunotherapy significantly improved pCR, MPR, and EFS, while AD immunotherapy significantly improved DFS in NSCLC patients compared to the control group. However, only PE immunotherapy significantly improved OS. Differences in efficacy between NE and PE across the entire population of resectable NSCLC remain to be explored in additional studies.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241284929"},"PeriodicalIF":4.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01eCollection Date: 2024-01-01DOI: 10.1177/17588359241285981
Fei Luo, Qiu-Zi Zhong, Xin Liu, Xiao-Rong Hou, Li-Ting Qian, Xue-Ying Qiao, Hua Wang, Yuan Zhu, Jian-Zhong Cao, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Mei Shi, Hui-Lai Zhang, Xi-Mei Zhang, Hang Su, Yu-Qin Song, Jun Zhu, Yu-Jing Zhang, Hui-Qiang Huang, Ying Wang, Xia He, Li-Ling Zhang, Bao-Lin Qu, Yong Yang, Chen Hu, Min Deng, Shu-Lian Wang, Shu-Nan Qi, Ye-Xiong Li
Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown.
Design: Retrospective cohort study.
Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations.
Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens.
Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW.
Conclusion: These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies.
{"title":"Optimizing the combination of chemotherapeutic drugs along with radiotherapy for extranodal NK/T-cell lymphoma.","authors":"Fei Luo, Qiu-Zi Zhong, Xin Liu, Xiao-Rong Hou, Li-Ting Qian, Xue-Ying Qiao, Hua Wang, Yuan Zhu, Jian-Zhong Cao, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Mei Shi, Hui-Lai Zhang, Xi-Mei Zhang, Hang Su, Yu-Qin Song, Jun Zhu, Yu-Jing Zhang, Hui-Qiang Huang, Ying Wang, Xia He, Li-Ling Zhang, Bao-Lin Qu, Yong Yang, Chen Hu, Min Deng, Shu-Lian Wang, Shu-Nan Qi, Ye-Xiong Li","doi":"10.1177/17588359241285981","DOIUrl":"https://doi.org/10.1177/17588359241285981","url":null,"abstract":"<p><strong>Background: </strong>Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Objectives: </strong>We screened multiple drug combinations to identify the most efficacious therapeutic combinations.</p><p><strong>Methods: </strong>We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens.</p><p><strong>Results: </strong>Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, <i>p</i> = 0.001), ASP/methotrexate-based (63.5%, <i>p</i> = 0.011), or ASP/not otherwise specified-based (63.2%, <i>p</i> < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW.</p><p><strong>Conclusion: </strong>These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241285981"},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1177/17588359241280692
Arian Mansur, Peiman Habibollahi, Adam Fang, Armeen Mahvash, Vahid Etezadi, Robert P Liddell, Juan C Camacho, Emil I Cohen, Nima Kokabi, Aravind Arepally, Christos Georgiades, Nariman Nezami
Radioembolization is a locoregional transarterial therapy that combines radionuclide and micron-sized beads to deliver radiation internally to the target tumors based on the arterial blood flow. While initially developed as a palliative treatment option, radioembolization is now used for curative intent treatment, neoadjuvant therapy, and method to downstage or bridge for liver transplant. Radioembolization has become increasingly utilized and is an important therapeutic option for the management of hepatocellular carcinoma and liver metastasis. This article provides an overview of the techniques, challenges, and novel developments in radioembolization, including new dosimetry techniques, radionuclides, and new target tumors.
{"title":"New frontiers in radioembolization.","authors":"Arian Mansur, Peiman Habibollahi, Adam Fang, Armeen Mahvash, Vahid Etezadi, Robert P Liddell, Juan C Camacho, Emil I Cohen, Nima Kokabi, Aravind Arepally, Christos Georgiades, Nariman Nezami","doi":"10.1177/17588359241280692","DOIUrl":"10.1177/17588359241280692","url":null,"abstract":"<p><p>Radioembolization is a locoregional transarterial therapy that combines radionuclide and micron-sized beads to deliver radiation internally to the target tumors based on the arterial blood flow. While initially developed as a palliative treatment option, radioembolization is now used for curative intent treatment, neoadjuvant therapy, and method to downstage or bridge for liver transplant. Radioembolization has become increasingly utilized and is an important therapeutic option for the management of hepatocellular carcinoma and liver metastasis. This article provides an overview of the techniques, challenges, and novel developments in radioembolization, including new dosimetry techniques, radionuclides, and new target tumors.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241280692"},"PeriodicalIF":4.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1177/17588359241282499
Sijia Wu, Junnan Xu, Yiwen Ma, Guilian Liang, Jiaxing Wang, Tao Sun
Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2- breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2- breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.
{"title":"Advances in the mechanism of CDK4/6 inhibitor resistance in HR+/HER2- breast cancer.","authors":"Sijia Wu, Junnan Xu, Yiwen Ma, Guilian Liang, Jiaxing Wang, Tao Sun","doi":"10.1177/17588359241282499","DOIUrl":"10.1177/17588359241282499","url":null,"abstract":"<p><p>Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2- breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2- breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241282499"},"PeriodicalIF":4.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-28eCollection Date: 2024-01-01DOI: 10.1177/17588359241277656
Annika Auranen, Matthew A Powell, Vladyslav Sukhin, Lisa M Landrum, Graziana Ronzino, Joseph Buscema, Dirk Bauerschlag, Roy Lalisang, David Bender, Lucy Gilbert, Amy Armstrong, Tamar Safra, Nicole Nevadunsky, Alexandra Sebastianelli, Brian Slomovitz, Kari Ring, Robert Coleman, Iwona Podzielinski, Ashley Stuckey, Michael Teneriello, Sarah Gill, Bhavana Pothuri, Lyndsay Willmott, Sudarshan Sharma, Christine Dabrowski, Grace Antony, Shadi Stevens, Mansoor Raza Mirza, Evelyn Fleming
Background: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.
Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.
Design: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.
Methods: Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.
Results: The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.
Conclusion: The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.
{"title":"Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).","authors":"Annika Auranen, Matthew A Powell, Vladyslav Sukhin, Lisa M Landrum, Graziana Ronzino, Joseph Buscema, Dirk Bauerschlag, Roy Lalisang, David Bender, Lucy Gilbert, Amy Armstrong, Tamar Safra, Nicole Nevadunsky, Alexandra Sebastianelli, Brian Slomovitz, Kari Ring, Robert Coleman, Iwona Podzielinski, Ashley Stuckey, Michael Teneriello, Sarah Gill, Bhavana Pothuri, Lyndsay Willmott, Sudarshan Sharma, Christine Dabrowski, Grace Antony, Shadi Stevens, Mansoor Raza Mirza, Evelyn Fleming","doi":"10.1177/17588359241277656","DOIUrl":"https://doi.org/10.1177/17588359241277656","url":null,"abstract":"<p><strong>Background: </strong>In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.</p><p><strong>Objectives: </strong>The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.</p><p><strong>Design: </strong>RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.</p><p><strong>Methods: </strong>Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.</p><p><strong>Results: </strong>The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.</p><p><strong>Conclusion: </strong>The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.</p><p><strong>Trial registration: </strong>NCT03981796.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241277656"},"PeriodicalIF":4.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.1177/17588359241281480
Jeong Uk Lim, Hye Seon Kang, Chang Dong Yeo, Ju Sang Kim, Sung Kyoung Kim, Jin Woo Kim, Seung Joon Kim, Sang Haak Lee
Background: Many patients with lung cancer have underlying chronic lung diseases. We assume that baseline lung functions might also affect the prognosis of non-small cell lung cancer (NSCLC) patients receiving immunotherapy.
Objectives: We aimed to assess the impact of pretreatment clinical parameters, including lung function measures such as forced vital capacity (FVC), on the prognosis of patients with NSCLC following immune checkpoint inhibitors (ICIs) therapy.
Design: Retrospective multicenter study.
Methods: Study subjects were consecutively selected from a multicenter cohort of patients with NSCLC who were undergoing immunotherapy. Patients were selected regardless of their initial cancer stage and prior treatment. The primary outcome was immunotherapy-related overall survival (iOS), defined as the duration from the initiation of immunotherapy to the time patients were censored. Spirometry values were acquired before bronchodilator application and were performed within the year before the first ICI treatment.
Results: We selected 289 patients for evaluation. The median iOS was 10.9 months (95% confidence interval (CI), 7.5-14.3). Programmed death-ligand 1 (PD-L1) expression, tested by SP263, was <1% in 20.9%, 1%-49% in 44.3%, and ⩾50% in 32.6% of the patients. ICI was used most often as second-line treatment (70.2%), followed by first line (13.1%), and third line (11.4%). In the Kaplan-Meier analysis, the median iOS of the low FVC group was significantly shorter than that in the preserved FVC group (6.10 (95% CI, 4.45-7.76) months vs 14.40 (95% CI, 10.61-18.34) months, p < 0.001)). A Cox regression analysis for iOS showed that age, poor performance status, PD-L1 expression measured by SP263, stage at diagnosis, and FVC (% predicted) were independent predictive factors. When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS.
Conclusion: Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities.
{"title":"Low pre-immunotherapy forced vital capacity is associated with poor outcomes in non-small cell lung cancer patients receiving immunotherapy regardless of prior treatment history.","authors":"Jeong Uk Lim, Hye Seon Kang, Chang Dong Yeo, Ju Sang Kim, Sung Kyoung Kim, Jin Woo Kim, Seung Joon Kim, Sang Haak Lee","doi":"10.1177/17588359241281480","DOIUrl":"10.1177/17588359241281480","url":null,"abstract":"<p><strong>Background: </strong>Many patients with lung cancer have underlying chronic lung diseases. We assume that baseline lung functions might also affect the prognosis of non-small cell lung cancer (NSCLC) patients receiving immunotherapy.</p><p><strong>Objectives: </strong>We aimed to assess the impact of pretreatment clinical parameters, including lung function measures such as forced vital capacity (FVC), on the prognosis of patients with NSCLC following immune checkpoint inhibitors (ICIs) therapy.</p><p><strong>Design: </strong>Retrospective multicenter study.</p><p><strong>Methods: </strong>Study subjects were consecutively selected from a multicenter cohort of patients with NSCLC who were undergoing immunotherapy. Patients were selected regardless of their initial cancer stage and prior treatment. The primary outcome was immunotherapy-related overall survival (iOS), defined as the duration from the initiation of immunotherapy to the time patients were censored. Spirometry values were acquired before bronchodilator application and were performed within the year before the first ICI treatment.</p><p><strong>Results: </strong>We selected 289 patients for evaluation. The median iOS was 10.9 months (95% confidence interval (CI), 7.5-14.3). Programmed death-ligand 1 (PD-L1) expression, tested by SP263, was <1% in 20.9%, 1%-49% in 44.3%, and ⩾50% in 32.6% of the patients. ICI was used most often as second-line treatment (70.2%), followed by first line (13.1%), and third line (11.4%). In the Kaplan-Meier analysis, the median iOS of the low FVC group was significantly shorter than that in the preserved FVC group (6.10 (95% CI, 4.45-7.76) months vs 14.40 (95% CI, 10.61-18.34) months, <i>p</i> < 0.001)). A Cox regression analysis for iOS showed that age, poor performance status, PD-L1 expression measured by SP263, stage at diagnosis, and FVC (% predicted) were independent predictive factors. When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS.</p><p><strong>Conclusion: </strong>Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241281480"},"PeriodicalIF":4.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.1177/17588359241279715
Shuting Zhan, Jianfu Li, Bo Cheng, Caichen Li, Yi Feng, Lei Fan, Shan Xiong, Wenchuang Zeng, Qi Cai, Yang Xiang, Huiting Wang, Chunyan Li, Peiling Chen, Xin Zheng, Wenhai Fu, Zhexue Hao, Jianxing He, Wenhua Liang
Background: Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited.
Objectives: This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+).
Design: A retrospective and observational study.
Methods: Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis.
Results: Data from 9785 NSCLC patients were collected. C-MET (-) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor (EGFR) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women (p < 0.001), early-stage (p = 0.003), adenocarcinoma (p < 0.001), and driver mutations (p < 0.001). Patients with anaplastic lymphoma kinase (ALK) alterations had a higher occurrence of C-MET overexpression positivity (57.1%). Positive C-MET overexpression was significantly associated with EGFR (p < 0.001), ALK (p < 0.001), and KRAS alterations (p = 0.024). Compared to C-MET overexpression (IHC 0), C-MET overexpression (IHC 2+) (hazard ratio (HR) = 0.455, p < 0.001) and C-MET overexpression (IHC 3+) (HR = 0.569, p < 0.001) were correlated with better overall survival in overall NSCLC patients, especially for C-MET overexpression (IHC 2+).
Conclusion: Our study elucidates the clinicomolecular characteristics and prognosis of C-MET overexpression in NSCLC patients, particularly those with positive C-MET overexpression (IHC 3+). This provides insight into the prevalence of C-MET overexpression in Chinese NSCLC patients and offers a basis for considering C-MET overexpression as a prognostic and predictive marker in NSCLC.
背景:关于非小细胞肺癌(NSCLC)患者C-MET蛋白过表达的真实世界数据有限,尤其是在亚洲华人群体中:关于非小细胞肺癌(NSCLC)患者C-MET蛋白过表达的真实世界数据有限,尤其是在亚洲华裔人群中:本研究旨在评估中国非小细胞肺癌患者C-MET蛋白过表达的临床分子特征和预后,重点关注C-MET蛋白过表达阳性(免疫组化(IHC)3+)的患者:设计:一项回顾性观察研究:数据来自2006年11月至2021年4月期间在广州医科大学附属第一医院确诊的NSCLC患者。我们使用IHC鉴定C-MET过表达,C-MET过表达阳性定义为IHC 3+且肿瘤细胞占50%。此外,还收集了患者的基因型以进行亚组分析:结果:共收集了9785名NSCLC患者的数据。C-MET(-)占5%(503/9785),C-MET(+)占27%(2654/9785),C-MET(++)占36%(3464/9785),C-MET(+++)占32%(3164/9785)。4326 名患者接受了基因检测。野生型占 37%(1591 例),表皮生长因子受体(EGFR)异常最常见,占 49%(2127 例)。C-MET 过表达阳性与女性有显著相关性(P P = 0.003),腺癌(P P ALK)改变的 C-MET 过表达阳性发生率更高(57.1%)。C-MET过表达阳性与表皮生长因子受体(EGFR)(p ALK)(p KRAS)改变明显相关(p = 0.024)。与C-MET过表达(IHC 0)相比,C-MET过表达(IHC 2+)(危险比(HR)= 0.455,p p 结论:我们的研究阐明了NSCLC患者C-MET过表达的临床分子特征和预后,尤其是C-MET过表达阳性(IHC 3+)的患者。这有助于了解C-MET过表达在中国NSCLC患者中的流行情况,并为将C-MET过表达作为NSCLC的预后和预测标志物提供依据。
{"title":"Landscape of C-MET overexpression in non-small cell lung cancer: a large-scale study of clinicomolecular features and prognosis based on Chinese data.","authors":"Shuting Zhan, Jianfu Li, Bo Cheng, Caichen Li, Yi Feng, Lei Fan, Shan Xiong, Wenchuang Zeng, Qi Cai, Yang Xiang, Huiting Wang, Chunyan Li, Peiling Chen, Xin Zheng, Wenhai Fu, Zhexue Hao, Jianxing He, Wenhua Liang","doi":"10.1177/17588359241279715","DOIUrl":"10.1177/17588359241279715","url":null,"abstract":"<p><strong>Background: </strong>Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited.</p><p><strong>Objectives: </strong>This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+).</p><p><strong>Design: </strong>A retrospective and observational study.</p><p><strong>Methods: </strong>Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis.</p><p><strong>Results: </strong>Data from 9785 NSCLC patients were collected. C-MET (-) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor (<i>EGFR</i>) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women (<i>p</i> < 0.001), early-stage (<i>p</i> = 0.003), adenocarcinoma (<i>p</i> < 0.001), and driver mutations (<i>p</i> < 0.001). Patients with anaplastic lymphoma kinase (<i>ALK</i>) alterations had a higher occurrence of C-MET overexpression positivity (57.1%). Positive C-MET overexpression was significantly associated with <i>EGFR</i> (<i>p</i> < 0.001), <i>ALK</i> (<i>p</i> < 0.001), and <i>KRAS</i> alterations (<i>p</i> = 0.024). Compared to C-MET overexpression (IHC 0), C-MET overexpression (IHC 2+) (hazard ratio (HR) = 0.455, <i>p</i> < 0.001) and C-MET overexpression (IHC 3+) (HR = 0.569, <i>p</i> < 0.001) were correlated with better overall survival in overall NSCLC patients, especially for C-MET overexpression (IHC 2+).</p><p><strong>Conclusion: </strong>Our study elucidates the clinicomolecular characteristics and prognosis of C-MET overexpression in NSCLC patients, particularly those with positive C-MET overexpression (IHC 3+). This provides insight into the prevalence of C-MET overexpression in Chinese NSCLC patients and offers a basis for considering C-MET overexpression as a prognostic and predictive marker in NSCLC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241279715"},"PeriodicalIF":4.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear.
Objectives: This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients.
Design: We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022.
Methods: Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome.
Results: More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells.
Conclusion: Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.
{"title":"Molecular features of NSCLC patients with liver metastasis.","authors":"Jun Zhao, Jia Zhong, Yujie Chen, Zipei Chen, Huan Yin, Yuange He, Rongrong Chen, Renhua Guo","doi":"10.1177/17588359241275421","DOIUrl":"https://doi.org/10.1177/17588359241275421","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear.</p><p><strong>Objectives: </strong>This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients.</p><p><strong>Design: </strong>We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022.</p><p><strong>Methods: </strong>Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome.</p><p><strong>Results: </strong>More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells.</p><p><strong>Conclusion: </strong>Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241275421"},"PeriodicalIF":4.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Pegylated liposomal doxorubicin (PLD), epirubicin and pirarubicin are the main anthracyclines widely used in China. PLD demonstrates therapeutic response comparable to epirubicin and pirarubicin in neoadjuvant chemotherapy (NAC) of breast cancer.
Objectives: The objectives of our study were to retrospectively assess the real-world effectiveness and prognostic characteristics of PLD as NAC for HR ⩽ 10%/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
Design: This was a retrospective study.
Methods: Our study enrolled patients with HR ⩽ 10%/HER2-negative breast cancer who received PLD-, epirubicin- or pirarubicin-based NAC from three centres in Hunan Province, China, between 2015 and 2022. We employed inverse probability of treatment weighting to balance the differences in patients' characteristics among the PLD, epirubicin, and pirarubicin groups. The endpoints were pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).
Results: A total of 267 patients were included. After NAC, the pCR rates in PLD group were superior to epirubicin group (PLD, 34.1%; epirubicin, 20.8%, p = 0.038). The differences in EFS (log-rank p = 0.99) and OS (log-rank p = 0.33) among the three groups were not statistically significant. Among the three groups, non-pCR patients had worse EFS than pCR patients (log-rank p = 0.014). For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups.
Conclusion: PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.
背景:聚乙二醇脂质体多柔比星(PLD)、表柔比星和吡拉比星是中国广泛使用的主要蒽环类药物。在乳腺癌新辅助化疗(NAC)中,PLD的治疗反应与表柔比星和吡柔比星相当:我们的研究旨在回顾性评估PLD作为HR⩽10%/人表皮生长因子受体2(HER2)阴性乳腺癌新辅助化疗的实际疗效和预后特征:这是一项回顾性研究:我们的研究纳入了中国湖南省三个中心在2015年至2022年间接受以PLD、表柔比星或吡拉比星为基础的新农合治疗的HR⩽10%/HER2阴性乳腺癌患者。我们采用了逆治疗概率加权法来平衡PLD组、表柔比星组和吡拉比星组之间患者特征的差异。研究终点为病理完全反应(pCR)、无事件生存期(EFS)和总生存期(OS):结果:共纳入 267 例患者。NAC后,PLD组的病理完全反应率优于表柔比星组(PLD,34.1%;表柔比星,20.8%,P = 0.038)。三组患者的 EFS(log-rank p = 0.99)和 OS(log-rank p = 0.33)差异无统计学意义。在三组患者中,非 pCR 患者的 EFS 差于 pCR 患者(log-rank p = 0.014)。对于pCR患者,三组的EFS(log-rank p = 0.47)和OS(log-rank p = 0.38)差异无统计学意义,PLD组非CR患者的EFS(log-rank p = 0.59)和OS(log-rank p = 0.14)与表柔比星组和吡拉比星组相似:结论:对于HR⩽10%/HER2阴性乳腺癌患者,与表柔比星或吡拉比星相比,PLD在新农合中具有相似的治疗反应和预后,这意味着PLD是一种潜在的新农合选择。
{"title":"Comparison of neoadjuvant chemotherapy response and prognosis among pegylated liposomal doxorubicin, epirubicin and pirarubicin in HR ⩽ 10%/HER2-negative breast cancer: an exploratory real-world multicentre cohort study.","authors":"Yue Hong, Jing Peng, Qitong Chen, Qin Zhou, Feng Xu, Jia Yao, Qiongyan Zou, Liqin Yuan, Lun Li, Qian Long, Liqiu Liao, Mingwen Liu, Xuan Liu, Danhua Zhang, Shouman Wang, Wenjun Yi","doi":"10.1177/17588359241279695","DOIUrl":"https://doi.org/10.1177/17588359241279695","url":null,"abstract":"<p><strong>Background: </strong>Pegylated liposomal doxorubicin (PLD), epirubicin and pirarubicin are the main anthracyclines widely used in China. PLD demonstrates therapeutic response comparable to epirubicin and pirarubicin in neoadjuvant chemotherapy (NAC) of breast cancer.</p><p><strong>Objectives: </strong>The objectives of our study were to retrospectively assess the real-world effectiveness and prognostic characteristics of PLD as NAC for HR ⩽ 10%/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.</p><p><strong>Design: </strong>This was a retrospective study.</p><p><strong>Methods: </strong>Our study enrolled patients with HR ⩽ 10%/HER2-negative breast cancer who received PLD-, epirubicin- or pirarubicin-based NAC from three centres in Hunan Province, China, between 2015 and 2022. We employed inverse probability of treatment weighting to balance the differences in patients' characteristics among the PLD, epirubicin, and pirarubicin groups. The endpoints were pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).</p><p><strong>Results: </strong>A total of 267 patients were included. After NAC, the pCR rates in PLD group were superior to epirubicin group (PLD, 34.1%; epirubicin, 20.8%, <i>p</i> = 0.038). The differences in EFS (log-rank <i>p</i> = 0.99) and OS (log-rank <i>p</i> = 0.33) among the three groups were not statistically significant. Among the three groups, non-pCR patients had worse EFS than pCR patients (log-rank <i>p</i> = 0.014). For patients with pCR, the differences in EFS (log-rank <i>p</i> = 0.47) and OS (log-rank <i>p</i> = 0.38) were not statistically significant among the three groups, and the EFS (log-rank <i>p</i> = 0.59) and OS (log-rank <i>p</i> = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups.</p><p><strong>Conclusion: </strong>PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241279695"},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}