Pub Date : 2024-04-04DOI: 10.1001/jamaoncol.2024.0207
D. Tougeron, L. Dahan, L. Evesque, K. Le Malicot, F. El hajbi, Thomas Aparicio, Olivier Bouché, N. Bonichon Lamichhane, B. Chibaudel, A. Angelergues, Anaïs Bodere, J. Phelip, M. Mabro, Laure Kaluzinski, C. Pétorin, G. Breysacher, Y. Rinaldi, A. Zaanan, Denis Smith, M. Gouttebel, Clément Perret, Nicolas Etchepare, Jean-François Emile, Ivan Sanfourche, Frédéric Di Fiore, C. Lepage, P. Artru, C. Louvet
Importance Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, Setting, and Participants The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and Measures The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%). Conclusions and Relevance Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial Registration ClinicalTrials.gov Identifier: NCT03959293.
{"title":"FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: The PRODIGE 59-FFCD 1707-DURIGAST Randomized Clinical Trial.","authors":"D. Tougeron, L. Dahan, L. Evesque, K. Le Malicot, F. El hajbi, Thomas Aparicio, Olivier Bouché, N. Bonichon Lamichhane, B. Chibaudel, A. Angelergues, Anaïs Bodere, J. Phelip, M. Mabro, Laure Kaluzinski, C. Pétorin, G. Breysacher, Y. Rinaldi, A. Zaanan, Denis Smith, M. Gouttebel, Clément Perret, Nicolas Etchepare, Jean-François Emile, Ivan Sanfourche, Frédéric Di Fiore, C. Lepage, P. Artru, C. Louvet","doi":"10.1001/jamaoncol.2024.0207","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0207","url":null,"abstract":"Importance\u0000Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited.\u0000\u0000\u0000Ojectives\u0000To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma.\u0000\u0000\u0000Design, Setting, and Participants\u0000The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy.\u0000\u0000\u0000Intervention\u0000Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023.\u0000\u0000\u0000Main outcome and Measures\u0000The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators.\u0000\u0000\u0000Results\u0000Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%).\u0000\u0000\u0000Conclusions and Relevance\u0000Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients.\u0000\u0000\u0000Trial Registration\u0000ClinicalTrials.gov Identifier: NCT03959293.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140744169","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 : 2024-04-04DOI: 10.1001/jamaoncol.2024.0234
M. Tachihara, Kayoko Tsujino
{"title":"Locally Advanced Relapse May Not Be Equal to Stage 3 Non-Small Cell Lung Cancer-Reply.","authors":"M. Tachihara, Kayoko Tsujino","doi":"10.1001/jamaoncol.2024.0234","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0234","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140741973","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 : 2022-10-13DOI: 10.1001/jamaoncol.2022.4445
Michael Webster-Clark, Alexander P Keil, Nicholas Robert, Jennifer R Frytak, Marley Boyd, Til Stürmer, Hanna Sanoff, Daniel Westreich, Jennifer L Lund
Importance: Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received.
Objective: To compare oxaliplatin delivery between MOSAIC trial participants and patients treated in the US Oncology Network with stage III colon cancer using a longitudinal cumulative dose (LCD).
Design, setting, and participants: This cohort study used secondary data from the MOSAIC trial, an international randomized clinical trial (concluded in 2004), and electronic health records from US Oncology (2009-2018), a network of community oncology practices in the US. It included participants in MOSAIC with stage III colon cancer who were randomized to receive treatment with oxaliplatin and fluorouracil/leucovorin (n = 663) and US Oncology patients with stage III colon cancer who were treated with a modified FOLFOX-6 regimen (n = 2523).
Exposures: Oxaliplatin and fluorouracil/leucovorin.
Outcomes and measures: We evaluated RDI and LCD over time and at the end of treatment in the MOSAIC and US Oncology populations. We used bootstrapping to estimate 95% confidence bands for LCD differences between the populations.
Results: The 663 MOSAIC participants (296 women [44.7%]) and 2523 US Oncology patients (1245 women [49.4%]) were generally similar with respect to demographic characteristics. Median RDI was lower in US Oncology (80% in MOSAIC vs 70% in US Oncology). The LCD also suggested differences in the total amount of oxaliplatin received between populations; the final median LCD in US Oncology was 10.2% lower than in MOSAIC, equivalent to receiving 1.2 fewer treatment cycles less of oxaliplatin. This difference only began 133 days into treatment and persisted after accounting for covariates, likely in terms of more frequent oxaliplatin treatment discontinuation in US Oncology patients than their MOSAIC counterparts.
Conclusions and relevance: The study results suggest that real-world patients in community practice in the US treated with modified FOLFOX 6 received less oxaliplatin than their historical counterparts in the MOSAIC trial, with differences manifesting late in the treatment course. The LCD allowed us to identify the amount and extent of these differences, the timing of which was unclear when using RDI alone.
{"title":"Comparing Trial and Real-world Adjuvant Oxaliplatin Delivery in Patients With Stage III Colon Cancer Using a Longitudinal Cumulative Dose.","authors":"Michael Webster-Clark, Alexander P Keil, Nicholas Robert, Jennifer R Frytak, Marley Boyd, Til Stürmer, Hanna Sanoff, Daniel Westreich, Jennifer L Lund","doi":"10.1001/jamaoncol.2022.4445","DOIUrl":"10.1001/jamaoncol.2022.4445","url":null,"abstract":"<p><strong>Importance: </strong>Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received.</p><p><strong>Objective: </strong>To compare oxaliplatin delivery between MOSAIC trial participants and patients treated in the US Oncology Network with stage III colon cancer using a longitudinal cumulative dose (LCD).</p><p><strong>Design, setting, and participants: </strong>This cohort study used secondary data from the MOSAIC trial, an international randomized clinical trial (concluded in 2004), and electronic health records from US Oncology (2009-2018), a network of community oncology practices in the US. It included participants in MOSAIC with stage III colon cancer who were randomized to receive treatment with oxaliplatin and fluorouracil/leucovorin (n = 663) and US Oncology patients with stage III colon cancer who were treated with a modified FOLFOX-6 regimen (n = 2523).</p><p><strong>Exposures: </strong>Oxaliplatin and fluorouracil/leucovorin.</p><p><strong>Outcomes and measures: </strong>We evaluated RDI and LCD over time and at the end of treatment in the MOSAIC and US Oncology populations. We used bootstrapping to estimate 95% confidence bands for LCD differences between the populations.</p><p><strong>Results: </strong>The 663 MOSAIC participants (296 women [44.7%]) and 2523 US Oncology patients (1245 women [49.4%]) were generally similar with respect to demographic characteristics. Median RDI was lower in US Oncology (80% in MOSAIC vs 70% in US Oncology). The LCD also suggested differences in the total amount of oxaliplatin received between populations; the final median LCD in US Oncology was 10.2% lower than in MOSAIC, equivalent to receiving 1.2 fewer treatment cycles less of oxaliplatin. This difference only began 133 days into treatment and persisted after accounting for covariates, likely in terms of more frequent oxaliplatin treatment discontinuation in US Oncology patients than their MOSAIC counterparts.</p><p><strong>Conclusions and relevance: </strong>The study results suggest that real-world patients in community practice in the US treated with modified FOLFOX 6 received less oxaliplatin than their historical counterparts in the MOSAIC trial, with differences manifesting late in the treatment course. The LCD allowed us to identify the amount and extent of these differences, the timing of which was unclear when using RDI alone.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT00275210.</p>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504962","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 : 2022-10-13DOI: 10.1001/jamaoncol.2022.4792
Lars Björnebo, Martin Eklund, Anna Lantz
{"title":"Association of 5α-Reductase Inhibitor Use With Prostate Cancer-Specific Mortality-Reply.","authors":"Lars Björnebo, Martin Eklund, Anna Lantz","doi":"10.1001/jamaoncol.2022.4792","DOIUrl":"10.1001/jamaoncol.2022.4792","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504845","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 : 2022-10-13DOI: 10.1001/jamaoncol.2022.4442
Stefania Canova, Stefano Arcangeli, Diego Luigi Cortinovis
{"title":"A Cast of Shadow on Postoperative Radiotherapy for pIIIA-N2 Non-Small Cell Lung Cancer?","authors":"Stefania Canova, Stefano Arcangeli, Diego Luigi Cortinovis","doi":"10.1001/jamaoncol.2022.4442","DOIUrl":"10.1001/jamaoncol.2022.4442","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33505407","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 : 2022-10-13DOI: 10.1001/jamaoncol.2022.4590
Kelsey L Corrigan, Michael Roth
{"title":"Treatment-Associated Breast Cancer Following Childhood Cancer: Where Do We Go From Here?","authors":"Kelsey L Corrigan, Michael Roth","doi":"10.1001/jamaoncol.2022.4590","DOIUrl":"10.1001/jamaoncol.2022.4590","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504844","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}
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