Survival analysis of KRAS, NRAS, BRAF, PIK3CA wild type (wt) mCRC patients treated with FOLFIRI plus cetuximab in the CAPRI-GOIM trial
The CAPRI-GOIM trial consisted of two parts: FOLFIRI plus cetuximab in first line followed by cetuximab plus FOLFOX as second line treatment for molecularly selected mCRC pts. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate and safety. This is an updated analysis providing the mature results for OS in KRAS, NRAS, BRAF, PIK3CA wt pts.
In the CAPRI-GOIM trial 340 mCRC pts with KRAS exon 2 wt tumors were treated in first line with FOLFIRI plus cetuximab until disease progression or unacceptable toxicity. After first line therapy progression, pts (157), who achieved a clinical response with first line treatment, were randomized to FOLFOX plus cetuximab (Arm A) or to FOLFOX (Arm B). Archival tissue samples from primary tumours were centrally assessed by next generation sequencing (NGS) with the Ion AmpliSeq Colon and Lung cancer panel. Here we report mature survival data at median follow-up of 69 months (m) (cut off date: April 30, 2017) for 98 out of the 124 RAS wt patients with NGS analysis, that were representative of the 340 intention to treat patient population.
Median OS for these 98 pts was 34.0 m (95% CI 30.2–37.8) with PFS of 11.7 m (95% CI 10.3–13.1). Eighty six out of 98 pts had tumors that were KRAS, NRAS, BRAF, PIK3CA wt. In this cohort, OS was 35.8 m (95% CI 29.9–41.9) with PFS of 12.3 m (95% CI 10.7–14.0). PFS and OS were also evaluated according to tumour location (see Table for results).
|Cohort||Median OS (months)
||Median PFS (months)
|RAS wt (n = 98)||33.4 (31.7- 34.9)||35.8 (29.9- 41.7)||9.9 (7.9- 12.0)||12.3 (11.0- 13.6)|
|KRAS, NRAS, BRAF, PIK3CA wt (n = 86)||34.0 (22.1- 46.0)||35.8 (29.5- 42.3)||9.9 (5.3- 14.6)||12.3 (10.7- 14.0)|
Long-term follow-up analysis of pts enrolled in the CAPRI-GOIM trial showed a median OS of approximately 36 m in KRAS, NRAS, BRAF and PIK3CA wt pts. A better prognostic outcome in terms of OS and PFS was observed in left-sided as compared to right-sided tumors.
Clinical trial identification
EudraCT number 2009-014041-81
Legal entity responsible for the study
Gruppo Oncologico dell'Italia Meridionale (GOIM)
Cetuximab was provided by Merck Serono. Other funding: AIRC
E. Martinelli: Advisory Board: Merck serono, Amgen. F. Ciardiello: Advisory Board: Merck Serono, Roche, Amgen, Pfizer, Bayer, Lilly. All other authors have declared no conflicts of interest.