Dr Cecchini on Etrumadenant-Based Combinations in Previously Treated mCRC

Michael Cecchini, MD, associate professor, medicine (medical oncology), co-director, Colorectal Program, Center for Gastrointestinal Cancers, medical oncology section lead, National Accreditation Program for Rectal Cancer, Internal Medicine, co-director, GI Clinical Research Team, Yale School of Medicine, discusses findings from the ARC-9 trial (NCT04660812) investigating an etrumadenant (AB928)–based combination regimen in patients with previously treated metastatic colorectal cancer (mCRC).

Cohort B of ARC-9 randomly assigned patients with mCRC to receive etrumadenant plus zimberelimab (AB122), mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), and bevacizumab (Avastin; n = 75) or regorafenib (Stivarga; n = 37). This trial yielded efficacy findings unlike any that have been seen in a randomized clinical trial of mCRC in the third-line setting, Cecchini begins. The study met its primary end point of progression-free survival (PFS). At a median follow-up of 20.4 months, the median PFS was 6.24 months (95% CI, 5.49-7.52) with the etrumadenant regimen vs 2.07 months (95% CI, 1.84-2.96) with regorafenib (HR, 0.27; 95% CI, 0.17-0.43; P < .001). The 6-month PFS rates in the etrumadenant and regorafenib arms were 54% and 6%, respectively. The 12-month PFS rates in these respective arms were 16% and 3%. This PFS benefit with etrumadenant vs regorafenib was observed across all analyzed patient subgroups, including geographic region, baseline ECOG performance status, baseline liver metastasis status, primary diagnosis, and primary tumor location.

Additionally, the median overall survival (OS) was 19.68 months (95% CI, 14.69-20.60) in the investigational arm vs 9.49 months (95% CI, 7.95-12.52) in the control arm (HR, 0.37; 95% CI, 0.22-0.63; P < .001). The 6-month OS rates in the etrumadenant and regorafenib arms were 90% and 71%, respectively. The 12-month PFS rates in these respective arms were 64% and 34%. The median OS was consistently longer in the etrumadenant arm vs the regorafenib arm across all analyzed subgroups.

The confirmed overall response rate was 17.3% in the etrumadenant arm vs 2.7% in the regorafenib arm. The median duration of response with etrumadenant was 11.5 months.