Alan Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Michelle Mahoney et al.
LBA10 - CALGB/SWOG 80405: Analysis of patients undergoing surgery as part of treatment strategy.
Patients with metastatic colorectal cancer may be cured with multimodality therapy. The goal of this subset analysis is to determine the characteristics and the long-term outcome of patients enrolled on this first-line treatment study for metastatic disease but who underwent surgery following chemotherapy.
Pts with KRAS wt (codons 12 and 13) MCRC and performance status 0-1 received FOLFIRI or mFOLFOX6 (MD/patient choice at enrollment) and randomized to either CET 400 mg/m2 X 1, then 250 mg/m2 qw or BV 5 mg/kg q2w. At enrollment, the goal of therapy was chosen by the MD: palliative or as neoadjuvant therapy as part of a curative treatment plan. Rx continued until progression, death, unacceptable toxicity, surgery with curative intent; treatment holidays of 4 weeks permitted but patients in general came off study if they underwent surgery. Subsequent Rx not mandated. Accrual goal was 1142 pts. 1° endpoint was overall survival (OS).
Between 11/2005 and 3/2012, 3058 unselected pts enrolled, 2334 KRAS wt pts randomized; final N =1137 (333 pre-amend eligible retrospective KRAS test, 804 post-amend), median follow-up = 32 mos; Median age–59 y; 61% male. At some point after chemotherapy, 179 patients (15.7%) went to surgery, median age 54, 62% male. 24.6% with intact primary, 36.9% with curative intent, 80% FOLFOX, and 58% CET. 130 of the 179 pts were NED immediately post-surgery (104 (58%) of these pts stopped protocol treatment to pursue surgery; 20 (11%) pts due to adverse events; 18 (10%) had surgery after progressing on study treatment. ) Median time between study entry and surgery was 6.8 mos and median OS from randomization was 60 mos; 95% CI (49, 69). DFS from surgical resection among NED pts was 16.1 mos; 95%CI (10.5, 22.2) and from randomization was 26 mos; 95% CI (21, 34). 96 pts are alive post-surgery (50 remain NED) after a median of 37 mos post-surgical f/u.
130 of 1137 pts enrolled on study reached NED after chemotherapy and surgery. The median OS in these patients was 60 months although many have recurred. We anticipate all-RAS status and plan on analyzing the subset of patients who underwent surgery to identify possible predictive characteristics and also to determine if there is an explanation for the fact that more patients on CET went to surgery than did pts on BV.