Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials

Abstract

Panitumumab is approved for RAS wild‐type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first‐line randomised studies. This retrospective analysis of these trials investigated efficacy and toxicity of panitumumab‐based maintenance after oxaliplatin discontinuation in RAS wild‐type patients. First‐line regimens were FOLFOX4 ± panitumumab in PRIME and mFOLFOX6 plus panitumumab or mFOLFOX6 plus bevacizumab in PEAK. Outcomes included median progression‐free survival (PFS) and overall survival (OS), from randomisation and oxaliplatin discontinuation, and toxicity. Overall, median duration of panitumumab plus 5‐fluorouracil/leucovorin (5‐FU/LV) maintenance was 21 (interquartile range: 11–41) weeks; that of 5‐FU/LV ± bevacizumab maintenance was 16 (6–31) weeks. Median OS from randomisation was 40.2 (95% confidence interval: 30.3–50.4) and 39.1 (34.2–63.0) months for panitumumab plus 5‐FU/LV maintenance and 24.1 (17.7–33.0) and 28.9 (21.0–32.0) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. Median PFS from randomisation was 16.6 (11.3–23.6) and 15.4 (11.6–18.4) months for panitumumab plus 5‐FU/LV maintenance and 12.6 (9.4–16.2) and 13.1 (9.5–16.6) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. From oxaliplatin discontinuation, median OS was 33.9 (24.7–42.8) and 33.5 (24.5–54.9) months for panitumumab plus 5‐FU/LV maintenance and 16.4 (12.4–24.1) and 23.3 (15.7–26.3) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively; PFS was 11.7 (7.8–19.2) and 9.7 (5.8–14.8) months and 7.1 (5.6–10.2) and 7.0 (3.9–10.6) months, respectively. The most frequently reported adverse events were rash, fatigue and diarrhoea. Maintenance of panitumumab plus 5‐FU/LV after oxaliplatin discontinuation was well tolerated and may be an acceptable treatment paradigm for patients demonstrating a good response to first‐line treatment. Prospective studies are warranted.

Comprehensive review of targeted therapy for colorectal cancer

“…89,90 Maintenance with panitumumab and 5-FU/LV after panitumumab plus FOLFOX showed numerical improvement in PFS and OS compared with single-agent panitumumab in the retrospective analysis of the PRIME and PEAK trials. 91 The toxicity of this combination did not increase, which was confirmed in the VALENTINO trial, in which maintaining single-agent panitumumab appeared to have shorter PFS (HR = 1.55, p = 0.011) than treatment with panitumumab combined with 5-FU/LV. 92 Cetuximab and panitumumab are both FDA-approved agents for the first-line treatment of CRC.…”

SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer

“…However, the VALENTINO study, comparing panitumumab monotherapy or 5-FU/LV plus panitumumab after eight cycles of induction therapy with FOLFOX plus panitumumab, showed that monotherapy was inferior in terms of 10-month PFS rates [16]. Similarly, a recent retrospective analysis of the PEAK and PRIME studies showed that maintenance with panitumumab plus 5-FU/LV after 11e12 cycles of an oxaliplatin-containing regimen was well tolerated and may be associated with better outcomes than strategies not containing panitumumab [17]. Thus, anti-EGFR antibody monotherapy may not be a suitable treatment option after oxaliplatin-based induction chemotherapy regarding efficacy.…”

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

“…PRIME and PEAK trials further analyzed the effects of panitumumab and fluorouracil/leucovorin (5-FU/LV) after panitumumab plus FOLFOX. The trials showed significant improvement in PFS and OS compared with panitumumab treatment alone [ 208 ]. In addition, the VALENTINO trial demonstrated synergistic effects of panitumumab with 5-FU/LV and better effects on outcome compared with treatment with panitumumab alone [ 209 ].…”