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.
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
Leone, Francesco;Silvestris, Nicola;
2023-01-01
Abstract
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.Pubblicazioni consigliate
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