Panitumumab in 1st Line in Older Patients – Results of the PANDA Study
The phase II PANDA study evaluated the regimens FOLFOX + panitumumab versus 5-FU + panitumumab in the 1st line treatment of patients with wt-RAS/BRAF metastatic colorectal cancer (mCRC).
Introduction
The available data regarding the efficacy of 1st line treatment in older patients are very limited. Many analyses adopt the controversial age limit of 65 years, and there are very few studies specifically dedicated to anti-EGFR agents. A therapeutic option for untreated metastatic colorectal cancer (mCRC) with wild type (wt) RAS oncogene is the FOLFOX + panitumumab (PAN) regimen. Guidelines recommend considering fluoropyrimidine monotherapy in elderly patients; however, no randomized study has explored the combination with EGFR antibodies in these cases.
Methodology and Study Course
This prospective open-label multicenter randomized study included patients aged ≥ 70 years with unresectable and untreated wt-RAS/BRAF mCRC. They were randomized to receive 12 cycles of FOLFOX + PAN (arm A) or 5-FU/leucovorin (LV) + PAN (arm B); followed by PAN maintenance therapy until disease progression (PD).
The primary endpoint was progression-free survival (PFS) in both arms. Stratification criteria included age (≤ 75 vs. > 75 years), ECOG performance status (0–1 vs. 2), and geriatric assessment using the G8 score (≤ 14 vs. > 14). The null hypothesis for median PFS ≤ 6 months was set in each therapeutic arm. No formal comparison of the evaluated arms was planned.
Study Population and Results
From July 2016 to April 2019, a total of 394 patients were screened, of which 211 were approved for study inclusion and 185 were randomized (92 in arm A and 93 in arm B). The main patient characteristics were comparable in both groups, with a median participant age of 77 years.
During the follow-up period (median 20.5 months), a total of 135 PD cases were recorded (64 in arm A, 71 in arm B). Median PFS was 9.6 months in arm A (95% confidence interval CI 8.8–10.9) and 9.1 months in arm B (95% CI 7.7–9.9). 65% of patients in arm A achieved a response to treatment, compared to 57% in arm B.
Observed grade 3–4 adverse events included neutropenia (9.8% of patients in arm A, 1.1% in group B), diarrhea (16.3% and 1.1%), stomatitis (9.8% and 4.4%), neurotoxicity (3.3% of patients in arm A), fatigue (6.5% and 4.4%), rash (25% and 24.2%), hypomagnesemia (3.3% and 7.7%).
Conclusions
Assuming multicenter cooperation, large prospective randomized studies of older patients diagnosed on a molecular level are feasible. The primary endpoint was met in both therapeutic arms. The combination of 5-FU/LV + panitumumab for 12 cycles followed by panitumumab maintenance until disease progression may be a justified therapeutic option for older patients with wt-RAS/BRAF mCRC. The authors recommend further evaluation in phase III studies.
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Source: Lonardi S., Schirripa M., Buggin F. et al. First-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS-BRAF wild-type metastatic colorectal cancer elderly patients: The PANDA study. J Clin Oncol 2020; 38 (suppl. 15): 4002, doi: 10.1200/JCO.2020.38.15_suppl.4002.
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