Maintenance therapy for mCRC is intended to prolong progression-free survival (PFS) with reduced toxicity, but little information is available concerning the value of epidermal growth factor receptor-targeted antibodies in this setting. Here we present data on outcomes of maintenance therapy from two first-line Pmab trials.
These retrospective analyses include data from patients with RAS WT (no mutations in KRAS or NRAS exons 2, 3 and 4) mCRC from two randomised trials: PRIME (Pmab + FOLFOX vs. FOLFOX) and PEAK (FOLFOX + either Pmab or bevacizumab). Maintenance therapy was defined as continuation of the other components of the patient’s study treatment after discontinuation of oxaliplatin. PFS and overall survival (OS) from baseline and from start of maintenance therapy were summarised for patients without progression in each treatment arm.
In PRIME and PEAK, 93 and 61 patients with RAS WT mCRC, respectively, received maintenance therapy (median [IQR] duration: PRIME, 16 [7–37] months; PEAK, 20 [13–41] months). Median PFS and OS overall and from start of maintenance therapy were longer in patients receiving Pmab maintenance vs. controls in both studies (Table).Table:
|Pmab + 5-FU maintenance (n = 52)||5-FU maintenance (n = 41)||Pmab + 5-FU maintenance (n = 31)||Bev + 5-FU maintenance (n = 30)|
|Survival from baseline, months (95% CI)|
|PFS||16.6 (11.3–23.6)||12.6 (9.4–16.2)||15.4 (11.6–18.4)||13.1 (9.5–16.6)|
|OS||40.2 (30.3–50.4)||24.1 (17.7–33.0)||39.1 (34.2–63.0)||28.9 (21.0–32.0)|
|Survival from start of maintenance, months (95% CI)|
|PFS||11.7 (7.8–19.2)||7.1 (5.6–10.2)||9.7 (5.8–14.8)||7.0 (3.9–10.6)|
|OS||33.9 (24.7–42.8)||16.4 (12.4–24.1)||33.5 (24.5–54.9)||23.3 (15.7–26.3)|
|Oxaliplatin cycles before maintenance therapy, median (range)||12 (2–31)||13 (5–41)||11 (3–21)||12 (3–19)|
|Restarted oxaliplatin during maintenance, n (%)||13 (25)||2 (5)||5 (16)||5 (17)|
5-FU, 5-fluorouracil; Bev, bevacizumab; CI, confidence interval; OS, overall survival; PFS, progression-free survival; Pmab, panitumumab
Even if time to oxaliplatin discontinuation is heterogeneous and patients receiving maintenance treatment are among those with greater treatment benefit, these retrospective data suggest that deintensification of Pmab-based treatment to 5-fluorouracil/Pmab maintenance is feasible and associated with extended PFS and OS. While maintenance is not part of the licensed indication for Pmab, physicians may drop oxaliplatin in patients with good initial response, to minimize toxicity, with the hypothesis that outcome would not be impacted. Ongoing prospective trials should confirm the value of Pmab maintenance and inform the design of future trials in which treatment strategy and sequence will be studied.
Clinical trial identification
PRIME: NCT00364013 PEAK: NCT00819780
Legal entity responsible for the study
F. Rivera Herrero: Advisory boards and/or received research funding from Amgen, Bayer, Celgene, Lilly, Merck Serono, MSD, Roche, Servier, and Sanofi. J-B. Bachet: Advisory boards and received research funding from Amgen, Bayer, Celgene, Merck Serono, Sanofi, and Servier. D.P. Modest: Honoraria and participated in advisory boards for Amgen, Bayer, Merck, MSD, Roche, Servier, and SIRTEX; travel support/research funding from Amgen, Bayer, Merck, Roche, and Servier. F. de Braud: Advisory boards and consultancy roles for Amgen, Eli Lilly, Merck Serono, Roche, and Servier. F. Pietrantonio: Advisory boards and consultancy roles for Amgen, Bayer, Eli-Lilly, Roche, and Sanofi. R. Koukakis: Employee of Amgen Ltd and owns restricted shares in Amgen. G. Demonty: Employee of Amgen (Europe) GmbH and owns restricted shares in Amgen. J-Y. Douillard: Steering committee involvement for Amgen and Bayer; advisory boards, symposia and consultancy for Amgen, Merck Serono, Roche, Sirtex and Takeda; advisory boards for Boehringer Ingelheim and Sanofi; and research funding from Merck Serono.