Clinical characterization and survival of patients (pts) with <i>PIK3CA</i> -mutated metastatic colorectal cancer (mCRC): Individual patient data (IPD) meta-analysis of four randomized trials.

Abstract

e15541 Background: We aimed to characterize pts with PIK3CA MUT mCRC and to estimate survival within an IPD meta-analysis of the randomized trials FIRE-1 (FUFIRI vs. mIROX), CIOX (CAPIRI or CAPOX plus Cetuximab), FIRE-3 (Cetuximab or Bevacizumab plus FOLFIRI) and PanaMa (FU/FA ±.Panitumumab after FOLFOX+Panitumumab). Methods: Kaplan-Meier estimated the progression-free (PFS) and overall survival (OS). Hazard ratios (HR) including the 95% confidence interval (CI) and interaction of PIK3CA status and treatment (anti-EGFR antibody vs. no anti-EGFR antibody) were assessed by adjusted multivariable Cox proportional hazard models (study, age, ECOG, primary tumor location). Discrete variables were compared by Fisher’s exact test. Results: In 107 of 920 tumors (11.6%), a PIK3CA MUT was detected. Concurrent RAS and BRAF MUT were found in n = 31 (29.0%) and n = 10 tumors (9.3%). A trend towards higher age ( P = 0.12), lower performance status ( P = 0.09) and right-sided primary tumors ( P = 0.14) was observed in PIK3CA MUT mCRC pts, in addition to atypical metastatic sites ( P = 0.047; other than liver, lung, nodes or peritoneum). Table 1 shows the median PFS and OS according to the PIK3CA status. In multivariate analyses, PIK3CA was not prognostically relevant for PFS ( P = 0.24), while a significant effect was observed for OS ( P &lt; 0.001). The use vs. omission of anti-EGFR antibodies was irrelevant for PFS, regardless of PIK3CA status (all-WT: HR 1.03, 95% CI 0.81 – 1.32, P = 0.80; PIK3CA MUT: HR 1.34, 95% CI 0.80 – 2.24, P = 0.27; interaction P = 0.41). OS, however, was significantly longer if anti-EGFR antibodies were applied in all-WT tumors (all-WT: HR 0.68, 95% CI 0.53 – 0.88, P = 0.003), while this was not the case for PIK3CA MUT tumors (HR 0.91, 95% CI 0.53 – 1.55, P = 0.73; interaction P = 0.067). Conclusions: This retrospective IPD meta-analysis indicates that PIK3CA mutation might have a prognostic relevance for mCRC and predictive implications for anti-EGFR treatment efficacy. Median PFS and OS according to PIK3CA status in four randomized trials (FIRE1, CIOX, FIRE3. PanaMa). Variable PFS(in months) OS(in months) RAS/BRAF WTPIK3CA WTn=493 9.4(8.8-10.0) 27.2(24.9-29.5) RAS/BRAF WTPIK3CA MUTn=66 8.8(7.6-10.0) 28.0(24.0-32.0) RAS MUTPIK3CA WTn=256 8.7(7.8-9.7) 21.1(18.0-24.2) RAS MUTPIK3CA MUTn=31 8.1(6.3-9.8) 18.5(12.0-25.0) BRAF MUTPIK3CA WTn=64 7.0(4.4-9.6) 15.9(11.7-20.1) BRAF MUTPIK3CA MUTn=10 5.8(4.0-7.5) 17.1(0.0-34.3) P 0.20 &lt;0.001