{"title":"帕尼单抗联合氟尿嘧啶、亚叶酸钙和奥沙利铂或联合氟尿嘧啶和亚叶酸钙治疗RAS和BRAF野生型转移性结直肠癌的老年患者:GONO基金会的PANDA试验","authors":"Sara Lonardi, Cosimo Rasola, Riccardo Lobefaro, Daniele Rossini, Vincenzo Formica, Mario Scartozzi, Giovanni Luca Frassineti, Giorgia Boscolo, Saverio Cinieri, Samantha Di Donato, Nicoletta Pella, Francesca Bergamo, Alessandra Raimondi, Ermenegildo Arnoldi, Lorenzo Antonuzzo, Cristina Granetto, Fable Zustovich, Monica Ronzoni, Silvana Leo, Federica Morano, Fotios Loupakis, Federica Buggin, Vittorina Zagonel, Matteo Fassan, Chiara Cremolini, Luca Boni, Filippo Pietrantonio","doi":"10.1200/JCO.23.00506","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with <i>RAS</i>/<i>BRAF</i> wild-type metastatic colorectal cancer (mCRC).</p><p><strong>Patients and methods: </strong>PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable <i>RAS</i>/<i>BRAF</i> wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time <b>≤</b>6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).</p><p><strong>Results: </strong>Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively (<i>P</i> < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.</p><p><strong>Conclusion: </strong>Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with <i>RAS</i>/<i>BRAF</i> wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"5263-5273"},"PeriodicalIF":42.1000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation.\",\"authors\":\"Sara Lonardi, Cosimo Rasola, Riccardo Lobefaro, Daniele Rossini, Vincenzo Formica, Mario Scartozzi, Giovanni Luca Frassineti, Giorgia Boscolo, Saverio Cinieri, Samantha Di Donato, Nicoletta Pella, Francesca Bergamo, Alessandra Raimondi, Ermenegildo Arnoldi, Lorenzo Antonuzzo, Cristina Granetto, Fable Zustovich, Monica Ronzoni, Silvana Leo, Federica Morano, Fotios Loupakis, Federica Buggin, Vittorina Zagonel, Matteo Fassan, Chiara Cremolini, Luca Boni, Filippo Pietrantonio\",\"doi\":\"10.1200/JCO.23.00506\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with <i>RAS</i>/<i>BRAF</i> wild-type metastatic colorectal cancer (mCRC).</p><p><strong>Patients and methods: </strong>PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable <i>RAS</i>/<i>BRAF</i> wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time <b>≤</b>6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).</p><p><strong>Results: </strong>Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively (<i>P</i> < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.</p><p><strong>Conclusion: </strong>Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with <i>RAS</i>/<i>BRAF</i> wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"5263-5273\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO.23.00506\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO.23.00506","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation.
Purpose: To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).
Patients and methods: PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable RAS/BRAF wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time ≤6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).
Results: Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively (P < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.
Conclusion: Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with RAS/BRAF wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.
期刊介绍：
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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