Pub Date : 2024-03-01Epub Date: 2024-03-08DOI: 10.1007/s11523-023-01023-y
Elias J Jabbour, Matthias Stelljes
Older patients with acute lymphoblastic leukemia (ALL) have historically had poor outcomes (5-year survival rate, 20%) with standard intensive and dose-adjusted chemotherapy regimens, due to a high incidence of adverse biologic features including high-risk cytogenetics, presence of TP53 mutations, and poor tolerance to intensive therapy. Thus, there is an unmet medical need in this patient population. Inotuzumab ozogamicin is a humanized antibody-drug conjugate that targets CD22-positive leukemic blasts. It is approved for the treatment of relapsed or refractory ALL and has been shown to be effective and tolerable in older patients. Several ongoing trials in older patients with newly diagnosed ALL have yielded encouraging data with inotuzumab ozogamicin in induction alone and in combination with low-intensity chemotherapy. In this podcast, the authors summarize and highlight some of the recent findings on the use of inotuzumab ozogamicin as induction therapy for older adults with newly diagnosed ALL.
{"title":"Inotuzumab in Older Patients with Newly Diagnosed Acute Lymphoblastic Leukemia-A Podcast.","authors":"Elias J Jabbour, Matthias Stelljes","doi":"10.1007/s11523-023-01023-y","DOIUrl":"10.1007/s11523-023-01023-y","url":null,"abstract":"<p><p>Older patients with acute lymphoblastic leukemia (ALL) have historically had poor outcomes (5-year survival rate, 20%) with standard intensive and dose-adjusted chemotherapy regimens, due to a high incidence of adverse biologic features including high-risk cytogenetics, presence of TP53 mutations, and poor tolerance to intensive therapy. Thus, there is an unmet medical need in this patient population. Inotuzumab ozogamicin is a humanized antibody-drug conjugate that targets CD22-positive leukemic blasts. It is approved for the treatment of relapsed or refractory ALL and has been shown to be effective and tolerable in older patients. Several ongoing trials in older patients with newly diagnosed ALL have yielded encouraging data with inotuzumab ozogamicin in induction alone and in combination with low-intensity chemotherapy. In this podcast, the authors summarize and highlight some of the recent findings on the use of inotuzumab ozogamicin as induction therapy for older adults with newly diagnosed ALL.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-01-30DOI: 10.1007/s11523-024-01035-2
Bi-Cheng Wang, Bo-Hua Kuang, Guo-He Lin
Background: Immunotherapy has revolutionized the treatment of hepatocellular carcinoma (HCC). However, whether adding immunotherapy to antiangiogenic therapy benefits patients with unresectable HCC (uHCC) more in the first-line setting remains controversial.
Objective: In this analysis, we compared the clinical outcomes of lenvatinib monotherapy with atezolizumab plus bevacizumab combination therapy in advanced uHCC in real-world clinical practice.
Methods: The MEDLINE, Embase, and Cochrane CENTRAL databases were systematically searched on 23 April 2023. The "metaSurvival" and "meta" packages of the R software (version 4.2.2) were used to summarize the survival curves and meta-analyze the survival data. Overall survival (OS) and progression-free survival (PFS) were defined as dual primary endpoints. Secondary endpoints included the objective response rate (ORR) and disease control rate (DCR).
Results: Overall, the pooled median OS was 18.4 months in the lenvatinib group versus 18.5 months in the atezolizumab plus bevacizumab group; the pooled median PFS was 6.9 months in the lenvatinib group versus 7.3 months in the atezolizumab plus bevacizumab group. Lenvatinib therapy showed similar OS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.55-1.52, p = 0.72] and PFS (HR: 0.79, 95% CI: 0.56-1.12, p = 0.19) compared with atezolizumab plus bevacizumab therapy. In addition, a comparable ORR [odds ratio (OR): 0.89, 95% CI: 0.65-1.20, p = 0.44) was observed between lenvatinib and atezolizumab plus bevacizumab.
Conclusions: Comprehensive analysis suggested that lenvatinib monotherapy exhibited survival outcomes comparable to those of atezolizumab plus bevacizumab combination therapy, which may provide useful insights for clinicians in future clinical practice.
{"title":"Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies.","authors":"Bi-Cheng Wang, Bo-Hua Kuang, Guo-He Lin","doi":"10.1007/s11523-024-01035-2","DOIUrl":"10.1007/s11523-024-01035-2","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has revolutionized the treatment of hepatocellular carcinoma (HCC). However, whether adding immunotherapy to antiangiogenic therapy benefits patients with unresectable HCC (uHCC) more in the first-line setting remains controversial.</p><p><strong>Objective: </strong>In this analysis, we compared the clinical outcomes of lenvatinib monotherapy with atezolizumab plus bevacizumab combination therapy in advanced uHCC in real-world clinical practice.</p><p><strong>Methods: </strong>The MEDLINE, Embase, and Cochrane CENTRAL databases were systematically searched on 23 April 2023. The \"metaSurvival\" and \"meta\" packages of the R software (version 4.2.2) were used to summarize the survival curves and meta-analyze the survival data. Overall survival (OS) and progression-free survival (PFS) were defined as dual primary endpoints. Secondary endpoints included the objective response rate (ORR) and disease control rate (DCR).</p><p><strong>Results: </strong>Overall, the pooled median OS was 18.4 months in the lenvatinib group versus 18.5 months in the atezolizumab plus bevacizumab group; the pooled median PFS was 6.9 months in the lenvatinib group versus 7.3 months in the atezolizumab plus bevacizumab group. Lenvatinib therapy showed similar OS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.55-1.52, p = 0.72] and PFS (HR: 0.79, 95% CI: 0.56-1.12, p = 0.19) compared with atezolizumab plus bevacizumab therapy. In addition, a comparable ORR [odds ratio (OR): 0.89, 95% CI: 0.65-1.20, p = 0.44) was observed between lenvatinib and atezolizumab plus bevacizumab.</p><p><strong>Conclusions: </strong>Comprehensive analysis suggested that lenvatinib monotherapy exhibited survival outcomes comparable to those of atezolizumab plus bevacizumab combination therapy, which may provide useful insights for clinicians in future clinical practice.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Non-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients.
Objective: We present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses.
Methods: This was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex® multiplex assay U-kit.
Results: Between January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month-not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor (p = 0.7), while it tended to be shorter in those with high levels of osteopontin (p = 0.05), angiopoietin-2 (p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 (p = 0.1).
Conclusions: This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment.
{"title":"A Phase II Study of FOLFIRI Plus Ziv-Aflibercept After Trifluridine/Tipiracil Plus Bevacizumab in Patients with Metastatic Colorectal Cancer: WJOG 11018G.","authors":"Toshihiko Matsumoto, Yoshiyuki Yamamoto, Masahito Kotaka, Toshiki Masuishi, Yasushi Tsuji, Hirokazu Shoji, Kenro Hirata, Takao Tsuduki, Akitaka Makiyama, Naoki Izawa, Naoki Takahashi, Masahiro Tsuda, Hisateru Yasui, Takashi Ohta, Yosuke Kito, Satoshi Otsu, Shuichi Hironaka, Kentaro Yamazaki, Narikazu Boku, Ichinosuke Hyodo, Kenichi Yoshimura, Kei Muro","doi":"10.1007/s11523-024-01043-2","DOIUrl":"10.1007/s11523-024-01043-2","url":null,"abstract":"<p><strong>Background: </strong>Non-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients.</p><p><strong>Objective: </strong>We present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses.</p><p><strong>Methods: </strong>This was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex<sup>®</sup> multiplex assay U-kit.</p><p><strong>Results: </strong>Between January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month-not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor (p = 0.7), while it tended to be shorter in those with high levels of osteopontin (p = 0.05), angiopoietin-2 (p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 (p = 0.1).</p><p><strong>Conclusions: </strong>This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment.</p><p><strong>Clinical trial registration: </strong>jRCTs041190100.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-03DOI: 10.1007/s11523-023-01031-y
Tomas Buchler, Alexandr Poprach
Several regimens combining immunotherapy and tyrosine kinase inhibitors (TKIs) have recently been validated for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). While immunotherapy is typically discontinued after 2 years in patients who neither progress nor experience limiting toxicity, according to the protocols of most recent phase III clinical trials, TKIs are to be continued until disease progression or the emergence of limiting toxicity. However, the prolonged use of TKIs is associated with significant toxicity and financial costs. This has sparked considerable debate about whether TKIs can be safely discontinued, particularly in mRCC patients who have achieved a verified complete response. This concise review examines the available evidence on TKI discontinuation in the context of mRCC management.
{"title":"Planned Discontinuation of Tyrosine Kinase Inhibitor Therapy in Metastatic Renal Cell Carcinoma: Lessons for the Era of Immunotherapy","authors":"Tomas Buchler, Alexandr Poprach","doi":"10.1007/s11523-023-01031-y","DOIUrl":"https://doi.org/10.1007/s11523-023-01031-y","url":null,"abstract":"<p>Several regimens combining immunotherapy and tyrosine kinase inhibitors (TKIs) have recently been validated for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). While immunotherapy is typically discontinued after 2 years in patients who neither progress nor experience limiting toxicity, according to the protocols of most recent phase III clinical trials, TKIs are to be continued until disease progression or the emergence of limiting toxicity. However, the prolonged use of TKIs is associated with significant toxicity and financial costs. This has sparked considerable debate about whether TKIs can be safely discontinued, particularly in mRCC patients who have achieved a verified complete response. This concise review examines the available evidence on TKI discontinuation in the context of mRCC management.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1007/s11523-023-01020-1
Xiuning Le, Eric Nadler, Daniel B Costa, John Victor Heymach
{"title":"Correction to: EGFR Tyrosine Kinase Inhibitors for the Treatment of Metastatic Non‑Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Podcast.","authors":"Xiuning Le, Eric Nadler, Daniel B Costa, John Victor Heymach","doi":"10.1007/s11523-023-01020-1","DOIUrl":"10.1007/s11523-023-01020-1","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138810984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Little is known regarding the prognostication of the Pan-Immune-Inflammation Value (PIV) in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Objectives: This study aimed to investigate the prognostic role of PIV in patients with R/M HNSCC receiving immune checkpoint inhibitors (ICI).
Patients and methods: Patients who were diagnosed to have R/M HNSCC and treated with ICI were reviewed retrospectively. The cutoff value of PIV was set at the median. Patients were stratified into high PIV and low PIV. Kaplan-Meier curves were estimated for progression-free survival (PFS) and overall survival (OS).
Results: A total of 192 patients were included in our study for oncologic outcomes evaluation. For the total population, the median PFS was 5.5 months and OS was 18.2 months. After stratification by PIV, median PFS was 11.7 months in the low PIV and 2.8 months in the high PIV groups (p < 0.001). The median OS was 21.8 months in the low PIV and 11.5 months in the high PIV groups (p < 0.001). Multivariate analysis demonstrated that PIV and PD-L1 were independent predictors associated with survival. A prognostic model using both PIV and PD-L1 was constructed. The median PFS was 12.2, 6.4, and 3.0 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001). The median OS was 23.7, 18.1, and 11.4 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001).
Conclusions: PIV is a prognostic biomarker in patients with R/M HNSCC treated with ICI. A prognostic model using PIV and PD-L1 could provide outcome prediction and risk stratification.
{"title":"A Novel Prognostic Model Using Pan-Immune-Inflammation Value and Programmed Death Ligand 1 in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Receiving Immune Checkpoint Inhibitors: A Retrospective Multicenter Analysis.","authors":"Ming-Yu Lien, Tzer-Zen Hwang, Chih-Chun Wang, Ching-Yun Hsieh, Chuan-Chien Yang, Chien-Chung Wang, Ching-Feng Lien, Yu-Chen Shih, Shyh-An Yeh, Meng-Che Hsieh","doi":"10.1007/s11523-023-01018-9","DOIUrl":"10.1007/s11523-023-01018-9","url":null,"abstract":"<p><strong>Background: </strong>Little is known regarding the prognostication of the Pan-Immune-Inflammation Value (PIV) in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).</p><p><strong>Objectives: </strong>This study aimed to investigate the prognostic role of PIV in patients with R/M HNSCC receiving immune checkpoint inhibitors (ICI).</p><p><strong>Patients and methods: </strong>Patients who were diagnosed to have R/M HNSCC and treated with ICI were reviewed retrospectively. The cutoff value of PIV was set at the median. Patients were stratified into high PIV and low PIV. Kaplan-Meier curves were estimated for progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>A total of 192 patients were included in our study for oncologic outcomes evaluation. For the total population, the median PFS was 5.5 months and OS was 18.2 months. After stratification by PIV, median PFS was 11.7 months in the low PIV and 2.8 months in the high PIV groups (p < 0.001). The median OS was 21.8 months in the low PIV and 11.5 months in the high PIV groups (p < 0.001). Multivariate analysis demonstrated that PIV and PD-L1 were independent predictors associated with survival. A prognostic model using both PIV and PD-L1 was constructed. The median PFS was 12.2, 6.4, and 3.0 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001). The median OS was 23.7, 18.1, and 11.4 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001).</p><p><strong>Conclusions: </strong>PIV is a prognostic biomarker in patients with R/M HNSCC treated with ICI. A prognostic model using PIV and PD-L1 could provide outcome prediction and risk stratification.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-11-22DOI: 10.1007/s11523-023-01016-x
Brigida Anna Maiorano, Ugo De Giorgi, Elena Verzoni, Evaristo Maiello, Giuseppe Procopio, Vincenza Conteduca, Massimo Di Maio
Background: PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations.
Objective: We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC.
Patients and methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs).
Results: Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected.
Conclusions: In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC.
{"title":"Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis.","authors":"Brigida Anna Maiorano, Ugo De Giorgi, Elena Verzoni, Evaristo Maiello, Giuseppe Procopio, Vincenza Conteduca, Massimo Di Maio","doi":"10.1007/s11523-023-01016-x","DOIUrl":"10.1007/s11523-023-01016-x","url":null,"abstract":"<p><strong>Background: </strong>PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations.</p><p><strong>Objective: </strong>We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC.</p><p><strong>Patients and methods: </strong>This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs).</p><p><strong>Results: </strong>Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected.</p><p><strong>Conclusions: </strong>In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Little is known regarding the association of cetuximab treatment beyond progression (TBP) with survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although immune checkpoint inhibitors (ICIs) are now considered as first-line treatment, not all patients are suitable for ICIs.
Objective: We conducted a multicenter, retrospective study to evaluate the role of cetuximab TBP in patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy.
Patients and methods: Patients with R/M HNSCC who had tumor progression after first-line cetuximab-containing chemotherapy were included into our study. Oncologic outcomes were estimated including time to cetuximab treatment discontinuation (TTD), progression-free survival 2 (PFS2), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Multivariate cox regression analysis with survival were conducted. Subgroup analysis with P16 and programmed death ligand 1 expression were performed.
Results: A total of 498 patients were eligible with 259 patients in the TBP group and 239 patients in the non-TBP group. The most common first-line chemotherapy was the EXTREME regimen in both groups. As for second-line treatment, the most common regimen were TPEx in the TBP group and taxane-based chemotherapy in the non-TBP group. Median TTD was 8.7 months in TBP and 5.5 months in non-TBP (p < 0.001). In terms of survival, median OS1 was significant longer in the TBP group than in the non-TBP group [14.1 months versus 10.9 months (p = 0.016)]. Multivariate analysis demonstrated cetuximab TBP was a factor independently associated with OS.
Conclusions: Our retrospective study suggests cetuximab TBP to be effective and to provide better survival for patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. Further prospective studies are warranted to validate the role of cetuximab TBP in R/M HNSCC.
{"title":"Cetuximab Treatment beyond Progression in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Nationwide Population-Based Study (THNS-2021-08).","authors":"Hung-Ming Wang, Pei-Jen Lou, Muh-Hwa Yang, Tein-Hua Chen, Ming-Yu Lien, Jin-Ching Lin, Jo-Pai Chen, Wei-Chen Lu, Hsueh-Ju Lu, Tai-Lin Huang, Chia-Jui Yen, Shang-Yin Wu, Hui-Ching Wang, Meng-Che Hsieh","doi":"10.1007/s11523-023-01028-7","DOIUrl":"10.1007/s11523-023-01028-7","url":null,"abstract":"<p><strong>Background: </strong>Little is known regarding the association of cetuximab treatment beyond progression (TBP) with survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although immune checkpoint inhibitors (ICIs) are now considered as first-line treatment, not all patients are suitable for ICIs.</p><p><strong>Objective: </strong>We conducted a multicenter, retrospective study to evaluate the role of cetuximab TBP in patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy.</p><p><strong>Patients and methods: </strong>Patients with R/M HNSCC who had tumor progression after first-line cetuximab-containing chemotherapy were included into our study. Oncologic outcomes were estimated including time to cetuximab treatment discontinuation (TTD), progression-free survival 2 (PFS2), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Multivariate cox regression analysis with survival were conducted. Subgroup analysis with P16 and programmed death ligand 1 expression were performed.</p><p><strong>Results: </strong>A total of 498 patients were eligible with 259 patients in the TBP group and 239 patients in the non-TBP group. The most common first-line chemotherapy was the EXTREME regimen in both groups. As for second-line treatment, the most common regimen were TPEx in the TBP group and taxane-based chemotherapy in the non-TBP group. Median TTD was 8.7 months in TBP and 5.5 months in non-TBP (p < 0.001). In terms of survival, median OS1 was significant longer in the TBP group than in the non-TBP group [14.1 months versus 10.9 months (p = 0.016)]. Multivariate analysis demonstrated cetuximab TBP was a factor independently associated with OS.</p><p><strong>Conclusions: </strong>Our retrospective study suggests cetuximab TBP to be effective and to provide better survival for patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. Further prospective studies are warranted to validate the role of cetuximab TBP in R/M HNSCC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-18DOI: 10.1007/s11523-023-01026-9
Nicole L France, Hannah A Blair
Tremelimumab (tremelimumab-actl; Imjudo®) is a monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). A single, priming dose of intravenous tremelimumab is used in combination with durvalumab, an ICI that blocks programmed cell-death ligand 1, in a regimen known as STRIDE (Single Tremelimumab Regular Interval Durvalumab). STRIDE is approved for the treatment of adults with unresectable hepatocellular carcinoma (HCC) in the USA and Japan and for the first-line treatment of adults with advanced or unresectable HCC in Europe. In the phase III HIMALAYA trial, STRIDE significantly improved overall survival (OS) compared with sorafenib in adults with unresectable HCC and no prior systemic therapy. A higher proportion of STRIDE versus sorafenib recipients had an objective response to treatment. The OS benefit associated with STRIDE was sustained with 4 years' follow-up. STRIDE had a manageable safety profile that differed from that of sorafenib. Grade 3 or 4 treatment-related adverse events occurred in a lower proportion of STRIDE versus sorafenib recipients. Based on the available evidence, tremelimumab used as part of the STRIDE regimen is a valuable first-line agent that expands the treatment options available to patients with advanced or unresectable HCC.
{"title":"Tremelimumab: A Review in Advanced or Unresectable Hepatocellular Carcinoma.","authors":"Nicole L France, Hannah A Blair","doi":"10.1007/s11523-023-01026-9","DOIUrl":"10.1007/s11523-023-01026-9","url":null,"abstract":"<p><p>Tremelimumab (tremelimumab-actl; Imjudo<sup>®</sup>) is a monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). A single, priming dose of intravenous tremelimumab is used in combination with durvalumab, an ICI that blocks programmed cell-death ligand 1, in a regimen known as STRIDE (Single Tremelimumab Regular Interval Durvalumab). STRIDE is approved for the treatment of adults with unresectable hepatocellular carcinoma (HCC) in the USA and Japan and for the first-line treatment of adults with advanced or unresectable HCC in Europe. In the phase III HIMALAYA trial, STRIDE significantly improved overall survival (OS) compared with sorafenib in adults with unresectable HCC and no prior systemic therapy. A higher proportion of STRIDE versus sorafenib recipients had an objective response to treatment. The OS benefit associated with STRIDE was sustained with 4 years' follow-up. STRIDE had a manageable safety profile that differed from that of sorafenib. Grade 3 or 4 treatment-related adverse events occurred in a lower proportion of STRIDE versus sorafenib recipients. Based on the available evidence, tremelimumab used as part of the STRIDE regimen is a valuable first-line agent that expands the treatment options available to patients with advanced or unresectable HCC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-11DOI: 10.1007/s11523-023-01024-x
James E Frampton
Pemigatinib (Pemazyre®), a selective, potent, reversible, oral inhibitor of fibroblast growth factor receptor (FGFR) 1-3, has received conditional (in the EU) or accelerated (in the USA) approval for the treatment of adults with previously treated, unresectable locally-advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 gene fusion or rearrangement. Over the course of a single-arm, phase 2 study (FIGHT-202), just over a third of patients with pretreated, advanced CCA [almost exclusively intrahepatic CCA (iCCA)] harbouring an FGFR2 fusion or rearrangement who received pemigatinib once daily (2 weeks on, 1 week off) had an objective response; nearly half had stable disease. Median progression-free survival and overall survival at the time of the final analysis were 7.0 months and 17.5 months, respectively. Pemigatinib was generally well tolerated and had a manageable safety profile. The most common treatment-related adverse event, hyperphosphataemia, was exclusively grade 1-2 in severity and, similarly, observed ocular and nail toxicities were rarely grade ≥ 3 in severity. Pending confirmation of its clinical benefits in an ongoing cisplatin plus gemcitabine-controlled, phase 3 study (FIGHT-302), pemigatinib provides a valuable targeted therapy for pretreated patients with advanced (i)CCA harbouring a FGFR2 fusion or rearrangement.
{"title":"Pemigatinib: A Review in Advanced Cholangiocarcinoma.","authors":"James E Frampton","doi":"10.1007/s11523-023-01024-x","DOIUrl":"10.1007/s11523-023-01024-x","url":null,"abstract":"<p><p>Pemigatinib (Pemazyre<sup>®</sup>), a selective, potent, reversible, oral inhibitor of fibroblast growth factor receptor (FGFR) 1-3, has received conditional (in the EU) or accelerated (in the USA) approval for the treatment of adults with previously treated, unresectable locally-advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 gene fusion or rearrangement. Over the course of a single-arm, phase 2 study (FIGHT-202), just over a third of patients with pretreated, advanced CCA [almost exclusively intrahepatic CCA (iCCA)] harbouring an FGFR2 fusion or rearrangement who received pemigatinib once daily (2 weeks on, 1 week off) had an objective response; nearly half had stable disease. Median progression-free survival and overall survival at the time of the final analysis were 7.0 months and 17.5 months, respectively. Pemigatinib was generally well tolerated and had a manageable safety profile. The most common treatment-related adverse event, hyperphosphataemia, was exclusively grade 1-2 in severity and, similarly, observed ocular and nail toxicities were rarely grade ≥ 3 in severity. Pending confirmation of its clinical benefits in an ongoing cisplatin plus gemcitabine-controlled, phase 3 study (FIGHT-302), pemigatinib provides a valuable targeted therapy for pretreated patients with advanced (i)CCA harbouring a FGFR2 fusion or rearrangement.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}