Nivolumab plus low-dose ipilimumab as first-line therapy in microsatellite instability-high/DNA mismatch repair deficient metastatic colorectal cancer: Clinical update.

Abstract

11 Background: In the phase 2 CheckMate 142 trial, nivolumab plus low-dose ipilimumab provided robust and durable clinical benefit and was well tolerated as first-line therapy for microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) (Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up data will be presented. Methods: Patients with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks until disease progression or discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR). Results: For all 45 patients (median follow-up was 13.8 months), ORR was 60% (95% CI 44.3–74.3). Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status (Table). Seven patients (16%) had grade 3–4 treatment-related adverse events; 3 (7%) had any grade treatment-related adverse events leading to discontinuation. Updated response, survival, and safety data after a longer follow-up (median 19.9 months) will be presented. Conclusions: Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated. Evaluated subgroups had responses consistent with the overall population. Nivolumab plus low-dose ipilimumab may represent a new first-line treatment option for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

Management of BRAF Gene Alterations in Metastatic Colorectal Cancer: From Current Therapeutic Strategies to Future Perspectives

“…In this trial, patients with BRAF -mutated mCRC were grouped into three arms; patients who received two or more lines of treatment were assigned to the nivolumab group (n = 25 patients) and patients who received one or more lines of treatment (n = 29 patients) or no prior treatment (n = 17 patients) were assigned to the nivolumab plus ipilimumab group. The response rates reported for these patients were 25%, 55%, and 76%, respectively, and were comparable to those for BRAF wild-type patients (41.4%, 55%, and 62%, respectively) ( 60 – 62 ). Therefore, BRAF -mutated mCRC with concomitant MSI-high should be preferred for treatment strategies according to the MSI-high status.…”

TremelImumab and Durvalumab Combination for the Non-OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-Arm, Multi-Cohort, Phase II INFINITY Study

“…In details, in the Checkmate 142 trial, the combination of nivolumab (3 mg/kg every 2 weeks) plus low-dose ipilimumab (1 mg/kg every 6 weeks), both given until disease progression or unacceptable toxicity, reached a 64% and 58% overall response rate (ORR) and 84% and 78% disease control rate (DCR) per investigator assessment and blinded central review, respectively. Moreover, median PFS and OS were not reached at the 19.9 months median follow up, with impressive 15-month PFS and OS rates of 75% and 84% [ 27 ]. Consistently, the phase III, randomized, open-label KEYNOTE-177 trial demonstrated the superiority of pembrolizumab as compared to standard chemotherapy in terms of PFS (median PFS 16.5 vs. 8.2 months, p = 0.0002) with a reduced toxicity burden [ 28 ].…”

Immune Checkpoint Inhibition as a Strategy in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer

“…[78] Several trials have demonstrated extremely encouraging response rates to immune checkpoint inhibition in patients with metastatic dMMR CRC, even those who were heavily pretreated (Table 2). [79][80][81][82][83][84][85][86] Moving treatment into the first-line setting has improved responses and using doublet immunotherapy treatment has increased response rates even further. For example, recent results from the Checkmate-142 trial reported an objective response rate of 69% in the first-line setting using dual-checkpoint inhibition for patients with dMMR CRC.…”