5FU / LV plus panitumumab for up to 12 cycles, followed by maintenance of panitumumab until disease progression may be a reasonable option in elderly patients with CCRm with wild-type RAS / BRAF tumors, seeking further investigation in phase III trials
PANDA is a prospective, multicenter, randomized, phase II trial that recruited patients aged ≥70 years who had unresectable or metastatic, RAS-BRAF wild-type colorectal cancer (CCRm) previously untreated.
PANDA is a prospective, multicenter, randomized phase II trial that recruited previously untreated wild-type RAS-BRAF metastatic or unresectable colorectal cancer (CCRM) patients ≥70 years of age.
Patients were randomly assigned to receive FOLFOX + panitumumab (arm A) or 5-FU / LV + panitumumab (arm B) for up to 12 cycles, followed by maintenance of panitumumab until disease progression.
The primary endpoint was progression-free survival (PFS) in both arms. Stratification criteria were age (≤ 75 versus> 75 years), ECOG PS (0–1 versus 2) and geriatric assessment with a G8 score (≤ 14 versus> 14).
In each treatment group, the null hypothesis for median PFS was established at ≤ 6 months. Assuming an average expected time of SLP ≥ 9.5 months with the two experimental schemes, a sample of 90 patients in each arm gave the study 90% power, with a type I error rate equal to 5% (unilateral Brookmeyer-Crowley) to reject the null hypothesis. No formal comparison between the two arms was planned.
From July 2016 to April 2019, a total of 394 patients were screened, 211 were considered eligible for inclusion and 185 were randomized (92 in arm A and 93 in arm B). The main characteristics of patients in arms A and B were, respectively: male 66% and 61%; mean age of 77 and 77 years; PS ≥ 1 49% and 55%; right colon 23% and 21%; G8> 14 31% and 30%.
In an average follow-up of 20.5 months, 135 disease progression events were observed (arms A and B: 64 and 71). The median PFS was 9.6 (95% CI 8.8-10.9) in arm A and 9.1 (95% CI 7.7-9.9) in arm B. Response rates were 65% and 57 % in arms A and B, respectively.
Grade 3-4 toxicities in arms A and B were neutropenia (9.8% and 1.1%), diarrhea (16.3% and 1.1%), mucositis (9.8% and 4.4%), neurotoxicity (3.3% and 0%), fatigue (6.5% and 4.4%), skin rash (25% and 24.2%) and hypomagnesaemia (3.3% and 7.7%).
Large prospective randomized trials in the elderly with molecularly selected colorectal cancer are possible with multi-center collaborative efforts. The primary outcome was achieved in both treatment groups. 5FU / LV plus panitumumab for up to 12 cycles, followed by maintenance of panitumumab until disease progression may be a reasonable option in elderly patients with colorectal cancer with wild-type RAS / BRAF tumors, seeking further investigation in phase III studies.
J Clin Oncol 38: 2020 (suppl; abstr 4002). DOI:10.1200/JCO.2020.38.15_suppl.4002