Second-Line Avelumab Improved PFS and Disease Control Among Patients With dMMR/MSI Metastatic Colorectal Cancer

According to results of a phase 2 trial, avelumab demonstrated better progression-free survival (PFS) and disease control duration among patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer, when compared with standard second-line treatment.

Julien Taïeb, MD, Hopital Européen Georges Pompidou, Paris, France, and coauthors wrote, “Although pembrolizumab is generally used as a first-line treatment, it still happens that patients are not tested for MMR IHC or MSI status upfront and are thus treated with standard first-line chemotherapy regiments with or without targeted agents and are referred to expert centers after a first-line treatment not containing an [immune checkpoint inhibitor].”

The open-label, phase 2 SAMCO-PRODIGE 54 trial enrolled 122 patients with dMMR/MSI metastatic colorectal cancer who had not received pembrolizumab in the first-line setting. Patients were randomized on a 1-to-1 basis to receive either 10 mg/kg avelumab every 2 weeks (n = 61), or investigator’s choice of second-line chemotherapy, with or without a targeted agent determined by first-line treatment regiment and RAS/BRAF status. Chemotherapy regimens included either modified FOLFOX-6 [leucovorin calcium, fluorouracil, and oxaliplatin] or FOLFIRI [leucovorin calcium, fluorouracil, and irinotecan hydrochloride] with or without either bevacizumab or cetuximab. The primary end point of the trial was PFS, with secondary end points including overall survival, overall response rate, time to best response, duration of disease control, and safety.

With a median follow-up duration of 33.3 months, the median PFS of patients in the avelumab arm was 4.1 months compared with 6.2 months in the chemotherapy arm. Because of features of the survival curves, alternative tests (Qiu and Sheng test) were used to determine avelumab as superior to chemotherapy with respect to PFS (P = .03). The 12-month PFS rate was 31.2% in the avelumab arm and 19.4% in the chemotherapy arm. The 18-mmonth PFS rate was 27.4% and 9.1%, respectively. Overall response rate and disease control rates were similar between the avelumab and chemotherapy arms. Among patients with disease control, the median duration of disease control was 16.7 months in the avelumab arm vs 7.3 in the chemotherapy arm (P < .001). Among patients with disease control, 18 in the avelumab group had ongoing disease control at 18 months, compared with 9 in the control group.

In the avelumab arm, there were 20 patients who experienced an adverse event of grade ≥3, compared with 34 in the chemotherapy group (P = .02). The most common grade ≥3 treatment-related adverse events in the avelumab arm were abnormal liver test results (7.9%), and diarrhea (4.8%); and in the chemotherapy arm were neutropenia (18.8%), fatigue (10.9%), hypertension (10.9%), and diarrhea (7.8%). There were no instances of grade 5 adverse events.

Dr Taïeb et al concluded this trial found, among patients with dMMR/MSI metastatic colorectal cancer who had not received pembrolizumab in the first line, “avelumab led to significantly longer PFS and fewer treatment-related adverse events than chemotherapy and justifies the use of [immune checkpoint inhibitors] in such patients rather than standard second-line treatments.”

Source:

Taïeb J, Bouche O, André T, et al. Avelumab vs standard second-line chemotherapy in patients with metastatic colorectal cancer and microsatellite instability. JAMA Oncol. Published August 3, 2023. doi:10.1001/jamaoncol.2023.2761