Pub Date : 2024-09-01Epub Date: 2024-06-05DOI: 10.1200/JCO.23.01959
Davide Soldato, Stefan Michiels, Julie Havas, Antonio Di Meglio, Martina Pagliuca, Maria Alice Franzoi, Barbara Pistilli, Neil M Iyengar, Paul Cottu, Florence Lerebours, Charles Coutant, Aurélie Bertaut, Oliver Tredan, Laurence Vanlemmens, Christelle Jouannaud, Iona Hrab, Sibille Everhard, Anne-Laure Martin, Fabrice André, Ines Vaz-Luis, Lee W Jones
Purpose: Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC.
Methods: Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 centers in France between 2012 and 2018 enrolled in the CANcer TOxicities study, with follow-up through October 2021. Exercise exposure was assessed using the Global Physical Activity Questionnaire-16, quantified in standardized metabolic equivalent of task-hours per week (MET-h/wk). We examined the dose/exposure response of pretreatment exercise on distant recurrence-free interval (DRFI) for all patients and stratified by clinical subtype and menopausal status using inverse probability treatment weighted multivariable Cox models to estimate hazard ratios (HRs).
Results: For the overall cohort, the relationship between exercise and DRFI was nonlinear: increasing exercise ≥ 5 MET-h/wk was associated with an inverse linear reduction in DRFI events up to approximately 25 MET-h/wk; increasing exercise over this threshold did not provide any additional DRFI benefit. Compared with <5 MET-h/wk, the adjusted HR for DRFI was 0.82 (95% CI, 0.61 to 1.00) for ≥ 5 MET-h/wk. Stratification by subtype revealed the hormone receptor-/human epidermal growth factor receptor 2- (HR-/HER2-; HR, 0.59 [95% CI, 0.38 to 0.92]) and HR-/HER2+ (HR, 0.37 [95% CI, 0.14 to 0.96]) subtypes were preferentially responsive to exercise. The benefit of exercise was observed especially in the premenopausal population.
Conclusion: Postdiagnosis/pretreatment exercise is associated with lower risk of DRFI events in a nonlinear fashion in primary BC; exercise has different impact on DRFI as a function of subtype and menopausal status.
{"title":"Dose/Exposure Relationship of Exercise and Distant Recurrence in Primary Breast Cancer.","authors":"Davide Soldato, Stefan Michiels, Julie Havas, Antonio Di Meglio, Martina Pagliuca, Maria Alice Franzoi, Barbara Pistilli, Neil M Iyengar, Paul Cottu, Florence Lerebours, Charles Coutant, Aurélie Bertaut, Oliver Tredan, Laurence Vanlemmens, Christelle Jouannaud, Iona Hrab, Sibille Everhard, Anne-Laure Martin, Fabrice André, Ines Vaz-Luis, Lee W Jones","doi":"10.1200/JCO.23.01959","DOIUrl":"10.1200/JCO.23.01959","url":null,"abstract":"<p><strong>Purpose: </strong>Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC.</p><p><strong>Methods: </strong>Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 centers in France between 2012 and 2018 enrolled in the CANcer TOxicities study, with follow-up through October 2021. Exercise exposure was assessed using the Global Physical Activity Questionnaire-16, quantified in standardized metabolic equivalent of task-hours per week (MET-h/wk). We examined the dose/exposure response of pretreatment exercise on distant recurrence-free interval (DRFI) for all patients and stratified by clinical subtype and menopausal status using inverse probability treatment weighted multivariable Cox models to estimate hazard ratios (HRs).</p><p><strong>Results: </strong>For the overall cohort, the relationship between exercise and DRFI was nonlinear: increasing exercise ≥ 5 MET-h/wk was associated with an inverse linear reduction in DRFI events up to approximately 25 MET-h/wk; increasing exercise over this threshold did not provide any additional DRFI benefit. Compared with <5 MET-h/wk, the adjusted HR for DRFI was 0.82 (95% CI, 0.61 to 1.00) for ≥ 5 MET-h/wk. Stratification by subtype revealed the hormone receptor-/human epidermal growth factor receptor 2- (HR-/HER2-; HR, 0.59 [95% CI, 0.38 to 0.92]) and HR-/HER2+ (HR, 0.37 [95% CI, 0.14 to 0.96]) subtypes were preferentially responsive to exercise. The benefit of exercise was observed especially in the premenopausal population.</p><p><strong>Conclusion: </strong>Postdiagnosis/pretreatment exercise is associated with lower risk of DRFI events in a nonlinear fashion in primary BC; exercise has different impact on DRFI as a function of subtype and menopausal status.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-06DOI: 10.1200/JCO.23.02717
Damon R Reed, Asmin Tulpule, Jonathan Metts, Matteo Trucco, Mark Robertson-Tessi, Tara J O'Donohue, Fiorella Iglesias-Cardenas, Michael S Isakoff, Audrey Mauguen, Neerav Shukla, Filemon S Dela Cruz, William Tap, Alex Kentsis, Carol D Morris, Meera Hameed, Joshua N Honeyman, Gerald G Behr, Maria Luisa Sulis, Michael V Ortiz, Emily Slotkin
ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.
治愈 ALL 需要多种 MRD 疗法。这一策略应推动转移性骨肉瘤的实验和试验。
{"title":"Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.","authors":"Damon R Reed, Asmin Tulpule, Jonathan Metts, Matteo Trucco, Mark Robertson-Tessi, Tara J O'Donohue, Fiorella Iglesias-Cardenas, Michael S Isakoff, Audrey Mauguen, Neerav Shukla, Filemon S Dela Cruz, William Tap, Alex Kentsis, Carol D Morris, Meera Hameed, Joshua N Honeyman, Gerald G Behr, Maria Luisa Sulis, Michael V Ortiz, Emily Slotkin","doi":"10.1200/JCO.23.02717","DOIUrl":"10.1200/JCO.23.02717","url":null,"abstract":"<p><p>ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-22DOI: 10.1200/JCO.23.02625
Marcin Dzienis, Juan Cundom, Christian Sebastian Fuentes, Anna Spreafico, Melanie Nordlinger, Andrea Viviana Pastor, Erin Alesi, Anterpreet Neki, Andrea S Fung, Iane Pinto Figueiredo Lima, Peter Oppelt, Geraldo Felicio da Cunha Junior, Barbara Burtness, Fabio Andre Franke, Jennifer E Tseng, Abhishek Joshi, Joy McCarthy, Ramona Swaby, Yulia Sidi, Burak Gumuscu, Niroshini Naicker, Gilberto de Castro
Purpose: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).
Methods: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator's choice of paclitaxel 100 mg/m2 on days 1 and 8 or 175 mg/m2 on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR.
Results: Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals.
Conclusion: Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.
{"title":"Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.","authors":"Marcin Dzienis, Juan Cundom, Christian Sebastian Fuentes, Anna Spreafico, Melanie Nordlinger, Andrea Viviana Pastor, Erin Alesi, Anterpreet Neki, Andrea S Fung, Iane Pinto Figueiredo Lima, Peter Oppelt, Geraldo Felicio da Cunha Junior, Barbara Burtness, Fabio Andre Franke, Jennifer E Tseng, Abhishek Joshi, Joy McCarthy, Ramona Swaby, Yulia Sidi, Burak Gumuscu, Niroshini Naicker, Gilberto de Castro","doi":"10.1200/JCO.23.02625","DOIUrl":"10.1200/JCO.23.02625","url":null,"abstract":"<p><strong>Purpose: </strong>Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).</p><p><strong>Methods: </strong>Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator's choice of paclitaxel 100 mg/m<sup>2</sup> on days 1 and 8 or 175 mg/m<sup>2</sup> on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR.</p><p><strong>Results: </strong>Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals.</p><p><strong>Conclusion: </strong>Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-24DOI: 10.1200/JCO.24.00863
Nico Gagelmann, Maximilian Merz
{"title":"Reply to Z. Yin et al.","authors":"Nico Gagelmann, Maximilian Merz","doi":"10.1200/JCO.24.00863","DOIUrl":"10.1200/JCO.24.00863","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-02DOI: 10.1200/JCO.23.02233
Andrea B Apolo, Daniel M Girardi, Scot A Niglio, Rosa Nadal, Andre R Kydd, Nicholas Simon, Lisa Ley, Lisa M Cordes, Elias Chandran, Seth M Steinberg, Sunmin Lee, Min-Jung Lee, Shraddha Rastogi, Nahoko Sato, Liang Cao, A Rouf Banday, Salah Boudjadi, Maria J Merino, Antoun Toubaji, Dilara Akbulut, Bernadette Redd, Hadi Bagheri, Rene Costello, Sandeep Gurram, Piyush K Agarwal, Heather J Chalfin, Vladimir Valera, Howard Streicher, John Joseph Wright, Elad Sharon, William D Figg, Howard L Parnes, James L Gulley, Biren Saraiya, Sumanta K Pal, David Quinn, Mark N Stein, Primo N Lara, Donald P Bottaro, Amir Mortazavi
Purpose: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.
Methods: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208).
Results: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.
Conclusion: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.
目的:在一项剂量递增I期研究中,卡博替尼(Cabozantinib)和尼韦单抗(nivolumab,CaboNivo)单独或与伊匹单抗(ipilimumab,CaboNivoIpi)联合治疗转移性尿路上皮癌(mUC)、转移性肾细胞癌(mRCC)和罕见泌尿生殖系统肿瘤(GU)患者显示出良好的疗效和安全性。我们报告了 I 期患者和 7 个扩展队列的安全性、总反应率 (ORR)、无进展生存期 (PFS) 和总生存期 (OS) 的最终数据分析:这是一项由研究者发起的多中心 I 期试验。CaboNivo双组扩展队列包括(1)mUC、(2)mRCC和(3)膀胱/泌尿道腺癌;CaboNivoIpi三组扩展队列包括(1)mUC、(2)mRCC、(3)阴茎癌和(4)膀胱鳞状细胞癌及其他罕见GU肿瘤(ClinicalTrials.gov标识符:NCT02496208):该研究共招募了120名接受CaboNivo(64人)或CaboNivoIpi(56人)治疗的患者,中位随访时间为49.2个月。在 108 例可评估的患者中(CaboNivo n = 59;CaboNivoIpi n = 49),ORR 为 38%(完全应答率为 11%),中位应答持续时间为 20 个月。mUC的ORR为42.4%,mRCC为62.5%(n=16),膀胱鳞状细胞癌为85.7%(n=7),阴茎癌为44.4%(n=9),肾髓样癌为50.0%(n=2)。84%的CaboNivo患者和80%的CaboNivoIpi患者发生了≥3级的治疗相关不良事件:结论:CaboNivo和CaboNivoIpi对多种GU恶性肿瘤患者具有临床活性和安全性,尤其是透明细胞RCC、尿路上皮癌和罕见GU肿瘤,如膀胱鳞状细胞癌、膀胱小细胞癌、膀胱腺癌、肾髓样癌和阴茎癌。
{"title":"Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.","authors":"Andrea B Apolo, Daniel M Girardi, Scot A Niglio, Rosa Nadal, Andre R Kydd, Nicholas Simon, Lisa Ley, Lisa M Cordes, Elias Chandran, Seth M Steinberg, Sunmin Lee, Min-Jung Lee, Shraddha Rastogi, Nahoko Sato, Liang Cao, A Rouf Banday, Salah Boudjadi, Maria J Merino, Antoun Toubaji, Dilara Akbulut, Bernadette Redd, Hadi Bagheri, Rene Costello, Sandeep Gurram, Piyush K Agarwal, Heather J Chalfin, Vladimir Valera, Howard Streicher, John Joseph Wright, Elad Sharon, William D Figg, Howard L Parnes, James L Gulley, Biren Saraiya, Sumanta K Pal, David Quinn, Mark N Stein, Primo N Lara, Donald P Bottaro, Amir Mortazavi","doi":"10.1200/JCO.23.02233","DOIUrl":"10.1200/JCO.23.02233","url":null,"abstract":"<p><strong>Purpose: </strong>Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.</p><p><strong>Methods: </strong>This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208).</p><p><strong>Results: </strong>The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.</p><p><strong>Conclusion: </strong>CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.
Patients and methods: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population.
Results: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]).
Conclusion: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.
{"title":"Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.","authors":"Huabin Hu, Jianwei Zhang, Yunfeng Li, Xiaozhong Wang, Ziqiang Wang, Hui Wang, Liang Kang, Ping Liu, Ping Lan, Xiaojian Wu, Yunhuan Zhen, Haiping Pei, Zhongcheng Huang, Hao Zhang, Wenbin Chen, Yongming Zeng, Jiajun Lai, Hongbo Wei, Xuefeng Huang, Jiansi Chen, Jigui Chen, Kaixiong Tao, Qingwen Xu, Xiang Peng, Junlin Liang, Guanfu Cai, Kefeng Ding, Zhijie Ding, Ming Hu, Wei Zhang, Bo Tang, Chuyuan Hong, Jie Cao, Zonghai Huang, Wuteng Cao, Fangqian Li, Xinhua Wang, Chao Wang, Yan Huang, Yandong Zhao, Yue Cai, Jiayu Ling, Xiaoyu Xie, Zehua Wu, Lishuo Shi, Li Ling, Hao Liu, Jianping Wang, Meijin Huang, Yanhong Deng","doi":"10.1200/JCO.23.01889","DOIUrl":"10.1200/JCO.23.01889","url":null,"abstract":"<p><strong>Purpose: </strong>The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.</p><p><strong>Patients and methods: </strong>OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population.</p><p><strong>Results: </strong>Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% <i>v</i> 94%), lymph node metastasis (pN1-2: 31% <i>v</i> 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]).</p><p><strong>Conclusion: </strong>NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-21DOI: 10.1200/JCO.24.00675
Heiko Schöder
{"title":"Machine Learning for Automated Interpretation of Fluorodeoxyglucose-Positron Emission Tomography Scans in Lymphoma.","authors":"Heiko Schöder","doi":"10.1200/JCO.24.00675","DOIUrl":"10.1200/JCO.24.00675","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-04DOI: 10.1200/JCO.23.02344
Mariana Chavez-MacGregor, Jieling Miao, Lajos Pusztai, Matthew P Goetz, Priya Rastogi, Patricia A Ganz, Eleftherios P Mamounas, Soonmyung Paik, Hanna Bandos, Wajeeha Razaq, Anne O'Dea, Virginia Kaklamani, Andrea L M Silber, Lisa E Flaum, Eleni Andreopoulou, Albert G Wendt, Jennifer F Carney, Priyanka Sharma, Julie R Gralow, Danika L Lew, William E Barlow, Gabriel N Hortobagyi
Purpose: Phosphatidylinositol 3-kinase/AKT-serine threonine kinase/mammalian target of rapamycin (mTOR) pathway abnormalities contribute to endocrine resistance. Everolimus, an mTOR inhibitor, improved progression-free survival in hormone receptor-positive metastatic breast cancer (BC) when combined with endocrine therapy (ET). In this phase III randomized, placebo-controlled trial, we assessed the efficacy of everolimus + ET as adjuvant therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC after adjuvant/neoadjuvant chemotherapy.
Methods: Patients were randomly assigned 1:1 to physician's choice ET and 1 year of everolimus (10 mg orally once daily) or placebo stratified by risk group. The primary end point was invasive disease-free survival (IDFS) evaluated by a stratified log-rank test with the hazard ratio (HR) estimated by Cox regression. Subset analyses included preplanned evaluation by risk group and exploratory analyses by menopausal status and age. Secondary end points included overall survival (OS) and safety. Everolimus did not improve IDFS/OS when added to ET in patients with early-stage high-risk, hormone receptor-positive BC.
Results: One thousand and nine hundred thirty-nine patients were randomly assigned with 1,792 eligible for analysis. Overall, no benefit of everolimus was seen for IDFS (HR, 0.94 [95% CI, 0.77 to 1.14]) or OS (HR, 0.97 [95% CI, 0.75 to 1.26]). The assumption of proportional hazards was not met suggesting significant variability in the HR over time since the start of treatment. In an unplanned subgroup analysis among postmenopausal patients (N = 1,221), no difference in IDFS (HR, 1.08 [95% CI, 0.86 to 1.36]) or OS (HR, 1.19 [95% CI, 0.89 to 1.60]) was seen. In premenopausal patients (N = 571), everolimus improved both IDFS (HR, 0.64 [95% CI, 0.44 to 0.94]) and OS (HR, 0.49 [95% CI, 0.28 to 0.86]). Treatment completion rates were lower in the everolimus arm compared with placebo (48% v 73%) with higher grade 3 and 4 adverse events (35% v 7%).
Conclusion: One year of adjuvant everolimus + ET did not improve overall outcomes. Subset analysis suggests mTOR inhibition as a possible target for patients who remain premenopausal after chemotherapy.
{"title":"Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.","authors":"Mariana Chavez-MacGregor, Jieling Miao, Lajos Pusztai, Matthew P Goetz, Priya Rastogi, Patricia A Ganz, Eleftherios P Mamounas, Soonmyung Paik, Hanna Bandos, Wajeeha Razaq, Anne O'Dea, Virginia Kaklamani, Andrea L M Silber, Lisa E Flaum, Eleni Andreopoulou, Albert G Wendt, Jennifer F Carney, Priyanka Sharma, Julie R Gralow, Danika L Lew, William E Barlow, Gabriel N Hortobagyi","doi":"10.1200/JCO.23.02344","DOIUrl":"10.1200/JCO.23.02344","url":null,"abstract":"<p><strong>Purpose: </strong>Phosphatidylinositol 3-kinase/AKT-serine threonine kinase/mammalian target of rapamycin (mTOR) pathway abnormalities contribute to endocrine resistance. Everolimus, an mTOR inhibitor, improved progression-free survival in hormone receptor-positive metastatic breast cancer (BC) when combined with endocrine therapy (ET). In this phase III randomized, placebo-controlled trial, we assessed the efficacy of everolimus + ET as adjuvant therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC after adjuvant/neoadjuvant chemotherapy.</p><p><strong>Methods: </strong>Patients were randomly assigned 1:1 to physician's choice ET and 1 year of everolimus (10 mg orally once daily) or placebo stratified by risk group. The primary end point was invasive disease-free survival (IDFS) evaluated by a stratified log-rank test with the hazard ratio (HR) estimated by Cox regression. Subset analyses included preplanned evaluation by risk group and exploratory analyses by menopausal status and age. Secondary end points included overall survival (OS) and safety. Everolimus did not improve IDFS/OS when added to ET in patients with early-stage high-risk, hormone receptor-positive BC.</p><p><strong>Results: </strong>One thousand and nine hundred thirty-nine patients were randomly assigned with 1,792 eligible for analysis. Overall, no benefit of everolimus was seen for IDFS (HR, 0.94 [95% CI, 0.77 to 1.14]) or OS (HR, 0.97 [95% CI, 0.75 to 1.26]). The assumption of proportional hazards was not met suggesting significant variability in the HR over time since the start of treatment. In an unplanned subgroup analysis among postmenopausal patients (N = 1,221), no difference in IDFS (HR, 1.08 [95% CI, 0.86 to 1.36]) or OS (HR, 1.19 [95% CI, 0.89 to 1.60]) was seen. In premenopausal patients (N = 571), everolimus improved both IDFS (HR, 0.64 [95% CI, 0.44 to 0.94]) and OS (HR, 0.49 [95% CI, 0.28 to 0.86]). Treatment completion rates were lower in the everolimus arm compared with placebo (48% <i>v</i> 73%) with higher grade 3 and 4 adverse events (35% <i>v</i> 7%).</p><p><strong>Conclusion: </strong>One year of adjuvant everolimus + ET did not improve overall outcomes. Subset analysis suggests mTOR inhibition as a possible target for patients who remain premenopausal after chemotherapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-06DOI: 10.1200/JCO.24.00720
D Ross Camidge, Jair Bar, Hidehito Horinouchi, Jonathan Goldman, Fedor Moiseenko, Elena Filippova, Irfan Cicin, Tudor Ciuleanu, Nathalie Daaboul, Chunling Liu, Penelope Bradbury, Mor Moskovitz, Nuran Katgi, Pascale Tomasini, Alona Zer, Nicolas Girard, Kristof Cuppens, Ji-Youn Han, Shang-Yin Wu, Shobhit Baijal, Aaron S Mansfield, Chih-Hsi Kuo, Kazumi Nishino, Se-Hoon Lee, David Planchard, Christina Baik, Martha Li, Peter Ansell, Summer Xia, Ellen Bolotin, Jim Looman, Christine Ratajczak, Shun Lu
Purpose: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.
Methods: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.
Results: In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).
Conclusion: Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.
{"title":"Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous <i>EGFR</i>-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.","authors":"D Ross Camidge, Jair Bar, Hidehito Horinouchi, Jonathan Goldman, Fedor Moiseenko, Elena Filippova, Irfan Cicin, Tudor Ciuleanu, Nathalie Daaboul, Chunling Liu, Penelope Bradbury, Mor Moskovitz, Nuran Katgi, Pascale Tomasini, Alona Zer, Nicolas Girard, Kristof Cuppens, Ji-Youn Han, Shang-Yin Wu, Shobhit Baijal, Aaron S Mansfield, Chih-Hsi Kuo, Kazumi Nishino, Se-Hoon Lee, David Planchard, Christina Baik, Martha Li, Peter Ansell, Summer Xia, Ellen Bolotin, Jim Looman, Christine Ratajczak, Shun Lu","doi":"10.1200/JCO.24.00720","DOIUrl":"10.1200/JCO.24.00720","url":null,"abstract":"<p><strong>Purpose: </strong>Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (<i>EGFR</i>)-wildtype NSCLC.</p><p><strong>Methods: </strong>Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous <i>EGFR</i>-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.</p><p><strong>Results: </strong>In total, 172 patients with nonsquamous <i>EGFR</i>-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).</p><p><strong>Conclusion: </strong>Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous <i>EGFR</i>-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-31DOI: 10.1200/JCO-24-01584
{"title":"Erratum: Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials.","authors":"","doi":"10.1200/JCO-24-01584","DOIUrl":"10.1200/JCO-24-01584","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}