One-year duration of nivolumab plus ipilimumab in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up of the GERCOR NIPICOL phase II study.

Abstract

13 Background: Optimal treatment duration with immune checkpoint inhibitors (ICI) for MSI/dMMR mCRC pts remains to be determined. Different durations are used, usually a fixed duration of 2 years or treatment until progression or toxicity. The GERCOR NIPICOL phase II study evaluated 1 year of therapy with nivolumab plus ipilimumab for MSI/dMMR mCRC pts. Here, we present the efficacy data with 16 months of additional follow-up since the primary analysis. Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidine, oxaliplatin, and irinotecan ± targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W for 4 cycles, then nivolumab 3 mg/kg Q2W until progression or a maximum of 20 cycles. Second course of nivolumab was permitted for pts who completed the predefined year of treatment and had later progressive disease (PD). Objectives were to evaluate response rates, progression-free survival (PFS) per iRECIST, and overall survival (OS). A landmark analysis was performed for PFS in pts who remained alive and progression-free at 1 year (theoretical end of treatment). Results: Of 57 pts included between Dec 2017 and Nov 2018, 36 (63%) completed the predefined 1-year duration of treatment. Reasons of premature treatment discontinuation were PD or death (n = 13), adverse event (n = 7), and the pt wish (n = 1). Overall median follow-up was 34.5 months. One, 2, and 3-year PFS rates were respectively 75.4% (95% CI 62.0-84.6), 70.0% (95% CI 56.2-80.1), and 70.0% (95% CI 56.2-80.1). One, 2, and 3-year OS rates were 84.1 (95% CI 71.7-91.4), 78.4% (95% CI 65.1-87.1), and 73.1% (95% CI 58.4-83.4), respectively. 42/57 pts were progression-free and alive at 1 year. Among them, median follow-up was 35.0 months and the 24-month PFS rate was 92.9% (95% CI 79.5-97.6%). PD was observed in three pts whose 12-month status was stable disease (SD). These three pts received a second course of nivolumab: two achieved PR and one had PD. Conclusions: Nivolumab plus ipilimumab with a fixed duration of 1 year continued to show durable activity in pts with chemoresistant MSI/dMMR mCRC after 3 years of follow-up. Reexposure to nivolumab seems to provide additional antitumor activity for pts experiencing late resistance after discontinuation of immunotherapy. Clinical trial information: NCT033501260.

How to overcome resistance to immune checkpoint inhibitors in colorectal cancer: From mechanisms to translation

“…115 In the GERCOR NIPICOL study, three dMMR mCRC patients who had PD after nivolumab plus ipilimumab received a second course of nivolumab; two of whom achieved PR. 116 These data suggest that re-exposure to anti-PD-1 therapy appears to provide additional antitumor activity in patients who developed acquired resistance to anti-PD-1 therapy. These data suggest that re-treatment with anti-PD-1 appears to increase anti-tumor activity in patients with acquired resistance to anti-PD-1 therapy.…”

“…In the KEYNOTE 164 study, nine dMMR mCRC patients who had progressive disease (PD) after pembrolizumab received a second course of pembrolizumab; six of whom achieved PR 115 . In the GERCOR NIPICOL study, three dMMR mCRC patients who had PD after nivolumab plus ipilimumab received a second course of nivolumab; two of whom achieved PR 116 . These data suggest that re‐exposure to anti‐PD‐1 therapy appears to provide additional antitumor activity in patients who developed acquired resistance to anti‐PD‐1 therapy.…”

Organ Preservation in Colon Cancer: An Illustrative Case Report

“…Consequently, we chose to observe her closely with serial ctDNA and CT scan rather than reintroducing immunotherapy. If she develops tumor recurrence, retreatment with ICI would be a consideration, as demonstrated in the GERCOR NIPICOL (Interest of iRECIST Evaluation for DCR for Evaluation of Patients With Deficient MMR and /or MSI Metastatic Colorectal Cancer Treated With Nivolumab and Ipilimumab) study [ 11 ].…”

Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy

“…The patients were administered nivolumab plus ipilimumab for one year. Three-year PFS and OS rates were 70% and 78%, respectively [ 204 ].…”