PURPOSETo 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 METHODSPANDA (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).RESULTSBetween 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.CONCLUSIONBoth 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.
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 / S. Lonardi, C. Rasola, R. Lobefaro, D. Rossini, V. Formica, M. Scartozzi, G.L. Frassineti, G. Boscolo, S. Cinieri, S. Di Donato, N. Pella, F. Bergamo, A. Raimondi, E. Arnoldi, L. Antonuzzo, C. Granetto, F. Zustovich, M. Ronzoni, S. Leo, F. Morano, F. Loupakis, F. Buggin, V. Zagonel, M. Fassan, C. Cremolini, L. Boni, F. Pietrantonio, G. Aprile, A. Ardizzoia, C. Aschele, E. Baldini, A. Ballestrero, A. Bertolini, R. Bordonaro, A. Buonadonna, M. Clavarezza, D. Corsi, E. Cortesi, F. De Braud, A. Falcone, A. Favaretto, L. Frassineti, A. Frassoldati, M. Frisinghelli, T. Gamucci, L. Gianni, F. Giovanardi, S. Gori, R. Grande, F. Leone, A. Luciani, C. Milandri, A. Sartore-Bianchi, N. Silvestris, E. Tamburini, G. Tomasello, G. Tonini, G. Tortora, C. Vergani, A. Zaniboni. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 41:34(2023), pp. 5263-5273. [10.1200/JCO.23.00506]
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
L. Boni;A. Ardizzoia;E. Baldini;F. De Braud;A. Sartore-Bianchi;
2023
Abstract
PURPOSETo 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 METHODSPANDA (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).RESULTSBetween 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.CONCLUSIONBoth 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.
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