Gastrointestinal, Colorectal

Post by Niel H. Segal, MD, PhD:

Colorectal cancer abstracts presented in poster discussion today focused on prognostic and predictive genomics, and combined modality treatment for localized rectal adenocarcinoma and anal squamous cell cancer. These studies do not change practice but are of much interest.

To identify a prognostic and predictive gene signature in localized colon cancer, Kerr et al. (#4000) used archival tissue from patients with stage II and III colon cancer enrolled in several prior clinical trials and performed RT-PCR identifying a set of 18 genes. This was then independently validated using patients enrolled in the QUASAR study, showing ability to prognosticate disease recurrence, disease free survival and overall survival in stage II colon cancer. This study supports personalized prognostic genomic analysis. However, it was not validated as a predictor of 5FU/L benefit. Tejpar et al. ( #4001) measured microsatellite instability (MSI-H) in patients enrolled in PETACC-3, treated with adjuvant infusional 5FU/L ± irinotecan. MSI-H status was identified as a prognostic factor for both recurrence and survival in patients with stage II and III colon cancer together. Subgroup analysis suggested a stronger effect in stage II than in stage III.

Two abstracts reported on the addition of oxaliplatin to neoadjuvant chemoradiation in localized rectal cancer. Aschele et al. (#CRA4008) reported a randomized phase III trial of standard preoperative radiation with infusional 5-FU alone or in combination with weekly oxaliplatin. Gerard and colleagues (#LBA4007), reported results from the ACCORD 12/0405 PRODIGE trial, in which patients were randomized to receive preoperative radiation with capecitabine, alone or in combination with weekly oxaliplatin. Neither trial supports the addition of oxaliplatin to the current dose and schedule of fluoropyrimidine-based chemotherapy, as this resulted in added toxicity without meaningful clinical benefit.

James et al. (#LBA4009) reported the ACT II study, a large multicenter, randomized factorial trial in localized anal squamous cell cancer to ask whether replacing mitomycin with cisplatin improves the complete response rate, and whether two cycles of maintenance chemotherapy after chemoradiation reduces recurrence. Treatment resulted in high complete response (95%) and recurrence free survival (75% at 3 yrs) rates. However, there was no difference in outcome by any treatment arm. Mitomycin resulted in more hematological toxicity without increased neutropenic fever. The combination of radiation with infusion 5-FU and mitomycin, without maintenance chemotherapy, remains the standard of care.