Summary
Long-term treatment with pembrolizumab was associated with durable responses and significant antitumor immunity over 3 years in patients with advanced colorectal cancer (CRC) and metastatic microsatellite instability-high (MSI-H) tumors who were enrolled in the phase II KEYNOTE-164 study. This is according study author Luis A. Diaz, MD, of the Memorial Sloan Kettering Cancer Center, who presented the findings from the trial at the ASCO 2020 Annual Meeting (Abstract 4032).
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Original Article
Pembrolizumab Effective, Produces Durable Responses Over 3 Years in MSI-H mCRC
Oncology Times
By Brandon May
Long-term treatment with pembrolizumab was associated with durable responses and significant antitumor immunity over 3 years in patients with advanced colorectal cancer (CRC) and metastatic microsatellite instability-high (MSI-H) tumors who were enrolled in the phase II KEYNOTE-164 study. This is according study author Luis A. Diaz, MD, of the Memorial Sloan Kettering Cancer Center, who presented the findings from the trial at the ASCO 2020 Annual Meeting (Abstract 4032).
The long-term KEYNOTE-164 data presented by Diaz at the ASCO 2020 event mirror those presented in previous publications of this trial, albeit with shorter follow-ups. The purpose of this analysis was to identify whether the responses continued beyond 2 years.
The KEYNOTE-164 trial (NCT02460198) was conducted at several sites across the globe. In this trial, a total of 124 patients with previously treated, unresectable MSI-H locally advanced or metastatic CRC (mCRC) were enrolled into two cohorts: patients who had received ≥2 prior lines of therapy (n=61) or those who have received ≥1 prior lines of therapy (n=63). Prior therapy lines included fluoropyrimidine, oxaliplatin, irinotecan, or anti-VEGF/EGFR. Only patients who had 3 years of follow-up data available and those who were retreated after disease progression were included in the analysis.
Patients received pembrolizumab 200 mg every 3 weeks for approximately 2 years, which represented a total of 35 treatment administrations. Treatment was administered for 2 years or until disease progression, unacceptable toxicity, or study withdrawal. Retreatment with up to 17 administrations in the second-course phase of the trial was reserved for patients who stopped treatment with pembrolizumab because of a confirmed complete response (CR) or if they had completed 2 years of treatment and progressed following cessation.
Diaz and colleagues assessed the objective response rate (ORR) to pembrolizumab over a median follow-up duration of 31.4 months (range = 0.2-47.8) among patients with ≥2 lines of prior therapy (cohort A) and over 36.1 months (range = 0.1-39.3) for patients with ≥1 prior line of therapy (cohort B). The ORR was assessed at the data cutoff of September 9, 2019. Additional outcomes included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety outcomes.
During follow-up, approximately 67% and 70% of patients in cohort A and cohort B discontinued pembrolizumab. Treatment discontinuation occurred mostly because of progressive disease.
In cohorts A and B, the ORRs were 32.8% (95% CI% 21.3-46.0) and 34.9% (95% CI 23.3-48.0), respectively. The median DOR was not reached (NR) in both cohorts A (range, 6.2-41.3+ months) and B (range, 3.9+ to 37.1+ months), suggesting treatment with pembrolizumab produced durable responses. At data cutoff, ongoing responses were observed in 15 patients in cohort A and 17 patients in cohort B.
Cohort A featured a median PFS of 2.3 months (95% CI 2.1-8.1) and a 3-year PFS rate of 31%. In cohort B, Diaz noted an almost double median PFS rate of 4.1 months (95% CI 2.1-18.9) but a somewhat similar 3-year PFS rate of 34% compared with cohort A. Cohort A had a median OS of 31.4 months (95% CI 21.4-NR), whereas the median OS in cohort B was NR (95% CI 19.2-NR). The 3-year OS rates in cohorts A and B were 49% and 52%, respectively.
A total of 6 patients in cohort A and 3 patients in cohort B received retreatment at the second-course phase. One patient in each cohort A and cohort B experienced a partial response. Approximately 16% of patients in cohort A and 13% of patients in cohort B experienced grade 3-4 drug-related adverse events. Any grade adverse events were observed in 64% of patients in cohort A and 70% of patients in cohort B. No grade 5 drug-related events and no drug-related deaths were observed during treatment.
Brandon May is a contributing writer.