ETS has been associated with improved long-term outcome in pts with KRAS/RAS-WT mCRC treated with first-line weekly cetuximab in the CRYSTAL, OPUS, and FIRE-3 studies. The present analysis evaluated the association between ETS and progression-free survival (PFS) and overall survival (OS) in the RAS-WT population from the Asia-Pacific, multicentre, nonrandomized, phase 2 APEC study.
APEC enrolled 289 pts with KRAS-WT tumours. Eligible pts received cetuximab every other week + FOLFOX or FOLFIRI (investigator's choice). Study treatment continued until disease progression, dose-limiting toxicity or consent withdrawal. RAS status was assessed retrospectively by ion torrent next-generation sequencing on evaluable samples. ETS was categorized as ≥20% decrease in the sum of longest diameters of target lesions between baseline and 8 weeks after start of treatment.
Median PFS and OS in the RAS-WT population (n = 167) were 13.0 and 28.4 months, respectively; the best confirmed objective response rate was 64.7% and 10.8% of pts were converted for R0 resection. ETS, as defined above, occurred in 81.8% (130/159) of evaluable pts and was associated with longer PFS and OS (Table). Although this study was not designed to formally assess efficacy differences between treatment subgroups, there were no major differences between pts receiving FOLFOX vs FOLFIRI. There were no unexpected safety findings.
|RAS-WT, ETS-Evaluable Pts||ETS (n = 130)||No ETS (n = 29)||Total (n = 159)|
|OS||# of events (%)||81 (62.3%)||20 (69.0%)||101 (63.5%)|
|HR (95% CI)||0.584 (0.357-0.954)||-|
|Median, mo (95% CI)||30.3 (26.3-33.2)||16.4 (10.3-31.2)||28.5 (24.5-32.3)|
|PFS||# of events (%)||90 (69.2%)||19 (65.5%)||109 (68.6%)|
|HR (95% CI)||0.721 (0.438-1.186)||-|
|Median, mo (95% CI)||14.0 (11.2-14.9)||7.5 (3.6-16.6)||13.3 (11.1-14.8)|
ETS at 8 weeks appears to be associated with longer PFS and OS in RAS-WT pts receiving FOLFOX or FOLFIRI + cetuximab every other week in the phase 2 APEC study. These findings are comparable to earlier subgroup analyses of analogous pivotal studies involving weekly cetuximab.
Clinical trial identification
G.H. Cornelio: Merck KGaA: receiving research funding. L. Shen, B. Ma: Merck KGaA: received honoraria. T.J. Prince, R. S.c. Lim: Merck KGaA: consulting. F. Beier: employee of Merck KGaA, Darmstadt, Germany. S. Chatterjee: employee of Merck Serono, Mumbai, India. All other authors have declared no conflicts of interest.