3525 Background: FIRE3 compared 1st-line therapy with FOLFIRI plus either cetuximab (arm A) or bevacizumab (arm B) in 592 patients (pts) with KRAS exon 2 wild-type metastatic colorectal cancer (mCRC). Second-line therapies appeared more successful in arm A compared to arm B. The impact of primary tumor location on this observation is unclear. Methods: Pts. were stratified for primary tumor site (left- vs. right-sided). Duration of 2nd-line therapy was calculated as time from first to last application. Progression-free survival (PFS2nd) and overall survival (OS2nd) of second-line therapy) were evaluated by Kaplan-Meier method and compared by log rank test as well as Cox regression. All analyses were performed in the RAS wild-type population of the trial and reported according to drug sequences. Results: 272 of 400 pts. (68%) received 2nd-line therapy, of those 206 (109 in arm A, 97 in arm B) pts. presented left-sided, whereas 66 (26 in arm A, 40 in arm B) pts. presented right-sided primaries. PFS2nd was markedly longer in pts. with left-sided as compared to right-sided primary tumors (6.0 (95% CI: 5.5-6.7) vs. 3.4 (95% CI: 3.0-5.8) months, hazard ratio (HR): 0.64 (95% CI: 0.47-0.87), P = 0.005). Differences in PFS2nd between study-arms were evident in pts. with left-sided primaries (arm A: 7.3 (95% CI: 6.4-7.7) vs. arm B: 5.3 (95% CI: 4.3-5.9) months, HR: 0.61 (95% CI: 0.44-0.84), P = 0.002), but not in pts. with right-sided primaries (arm A: 4.0 (95% CI: 3.0-6.3) vs. arm B: 3.3 (95% CI: 2.6-5.8) months, HR: 1.09 (95% CI: 0.62-1.90). Consistent observations were also made for treatment duration and OS2nd. Conclusions: This retrospective analysis indicates that treatment duration and efficacy of second-line therapy are associated with primary tumor location. Efficacy of second-line therapy was significantly greater in pts. with left-sided tumors as compared to right sided tumors. This difference was driven by superior activity of second-line regimens of arm A compared to arm B in left-sided tumors. Our observations confirm the strong prognostic value of primary tumor location in mCRC across treatment lines. Clinical trial information: NCT00433927.
Predictive value of primary tumor location: Results from randomized phase II study of panitumumab + irinotecan versus cetuximab + irinotecan in patients with KRAS exon2 wild-type metastatic colorectal cancer (WJOG6510G)
