In an analysis of the German phase II PanaMa trial reported in the Journal of Clinical Oncology, Stahler et al evaluated consensus molecular subtypes as prognostic and predictive biomarkers in patients with RAS wild-type metastatic colorectal cancer receiving fluorouracil and leucovorin with or without panitumumab maintenance after panitumumab plus mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) induction.
The interaction of consensus molecular subtypes with outcomes were assessed among 296 patients (CMS population) in the safety set (n = 377) who received induction therapy and had available consensus molecular subtype data. The interactions with outcomes were analyzed in the full analysis set of 196 patients who also received maintenance.
Key Findings
In the CMS population, CMS1 was found in 29 patients (9.8%), CMS2 in 122 patients (41.2%), CMS3 in 33 patients (11.2%), and CMS4 in 112 (37.8%). Consensus molecular subtype was unclassifiable in 17 (5.7%).
Consensus molecular subtypes were prognostic biomarkers for progression-free survival (overall P < .0001), overall survival (overall P < .0001), and objective response rate (overall P = .02) since the start of induction treatment. Tumors classified as CMS2 or CMS4 were associated with the longest progression-free survival and overall survival and highest response rate, whereas CMS1 and CMS3 tumors were associated with the shortest survival outcomes.
In the full analysis set, the addition of panitumumab to fluorouracil/leucovorin maintenance was associated with at least numerically longer progression-free survival (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.36–0.95, P = .03) and overall survival (HR = 0.88, 95% CI = 0.52–1.52, P = .66) among patients with CMS2 tumors; these trends in progression-free survival (HR = 0.63, 95% CI = 0.38-1.03, P = .07) and overall survival (HR = 0.54, 95% CI = 0.30-0.96, P = .04) were similar among patients with CMS4 tumors. In contrast, the addition of panitumumab to maintenance therapy was associated with detrimental impact on progression-free survival, overall survival, and objective response rate in patients with CMS1 tumors and those with CMS3 tumors.
On multivariate analysis, the significant interaction of treatment with consensus molecular subtype was confirmed for progression-free survival (CMS2 vs CMS1/3, P = .02; CMS4 vs CMS1/3, P = .03) and overall survival (CMS2 vs CMS1/3, P = .03; CMS4 vs CMS1/3, P < .001).
The investigators concluded, “The consensus molecular subtype had a prognostic impact on progression-free survival, overall survival, and objective response rate in RAS wild-type metastatic colorectal cancer. In PanaMa, panitumumab plus [fluorouracil/leucovorin] maintenance was associated with beneficial outcomes in CMS2/4, whereas no benefit was observed in CMS1/3 tumors.”
Arndt Stahler, MD, of the Division of Hematology, Oncology and Tumor Immunology, Charité Universitaetsmedizin Berlin, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The trial was supported by the AIO-Studien-gGmbH and Amgen Inc. For full disclosures of the study authors, visit ascopubs.org.
