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Nivolumab plus standard-of-care does not meet primary endpoint for mCRC

Presented by
Dr Heinz-Josef Lenz, USC Norris Comprehensive Cancer Center, CA, USA
ASCO GI 2022
Phase 3, CheckMate 9X8
In the phase 2/3 CheckMate 9X8 trial, nivolumab plus standard-of-care did not significantly improve progression-free survival (PFS) compared with standard-of-care alone in the first-line treatment of patients with metastatic colorectal cancer (mCRC). However, the results numerically favoured patients receiving additional nivolumab. Moreover, exploratory analyses revealed that patients with CMS1 and CMS3 molecular subtypes, or CD8 levels ≥2% displayed benefits from nivolumab [1].

“The efficacy of standard therapies in patients with mCRC may be enhanced by the addition of an immunotherapeutic agent,” Dr Heinz-Josef Lenz (USC Norris Comprehensive Cancer Center, CA, USA) explained. The phase 2/3 CheckMate 9X8 trial (NCT03414983) investigated whether nivolumab, a PD-1 inhibitor, may deliver patient benefits when added to first-line standard-of-care. Patients with mCRC were randomised to nivolumab 240 mg every 2 weeks plus mFOLFOX6/bevacizumab (n=127) or mFOLFOX6/bevacizumab alone (n=68). The primary endpoint was PFS.

The primary endpoint was not met, with the median PFS reaching 11.9 months in both treatment arms. However, PFS rates after 12 months were numerically higher in patients receiving nivolumab than in patients receiving standard-of-care only, with 15-month PFS rates of 45% and 21.5%, and 18-months PFS rates of 28% and 9%, respectively. Subgroup analyses numerically favoured the nivolumab arm over the standard-of-care arm across all pre-defined subgroups. Furthermore, the objective response rate was numerically higher in the nivolumab arm (60% vs 46%) and the median duration of response was longer for patients on nivolumab (12.9 vs 9.3 months). Also, exploratory analyses showed that CMS1 and CMS3 subsets of patients were likely to benefit more from nivolumab, as well as patients who displayed CD8 levels ≥2%. Further studies are warranted to select patients that may benefit from this novel regimen.

No new safety issues were identified and the safety profile of nivolumab plus standard-of-care was acceptable, according to Dr Lenz. The rate of grade 3 or 4 adverse events (AEs) was higher in the nivolumab arm than in the standard-of-care arm (75% vs 48%). The most common grade 3 or 4 AEs among nivolumab receivers were neutropenia (26%), decreased neutrophil count (20%), and diarrhoea (7%). Any grade immune-related AEs in the nivolumab arm were predominantly of gastrointestinal (42%), endocrine (22%), or dermatologic (27%) origin.

  1. Lenz H-J, et al. Nivolumab + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab versus mFOLFOX6/bevacizumab for first-line treatment of metastatic colorectal cancer: phase 2 results from CheckMate Abstract 8, ASCO GI 2022, 20–22 January.


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