According to the results of the phase 2 KEYNOTE-629 trial, patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma appear to receive promising anti-tumor benefit from pembrolizumab.
Notable and long-lasting antitumor activity was observed in a population of patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma (cSCC) who were treated with pembrolizumab (Keytruda), according to the results of the phase 2 KEYNOTE-629 trial (NCT03284424).
Data from the trial indicated that the locally advanced cohort had an overall response rate (ORR) of 50.0% (95% CI, 36.1%-63.9%), with 27 of 54 patients obtaining a confirmed response. Within this population, 16.7% of patients achieved a complete response (CR; n = 9) and 18 experienced a partial response (PR; n = 18). Among those with recurrent/metastatic melanoma, patients who were treated with pembrolizumab experienced an ORR of 35.2% (95% CI, 26.2%-45.2%), including a CR rate of 35.2% (n = 11) and a PR rate of 24.8% (n = 26).
The multicenter, non-randomized, single arm, open label study was conducted at 59 centers across 10 countries. To enroll, patients needed to be 18 years old or older with histologically confirmed locally advanced or relapsed/recurrent disease. An ECOG performance status of 0 or 1 was required. Those within the locally advanced cohort needed to be ineligible for surgical resection and have previously undergone or were ineligible for radiation therapy. Additionally, the recurrent/metastatic cohort either had locoregional recurrent disease that was not amenable to surgery or radiation, or distant metastases.
Patients who enrolled on the trial were treated with pembrolizumab for 35 cycles—approximately 2 years—or until they experienced disease progression, unacceptable toxicity, consent withdrawal, investigator decision, or other criteria were met.
The primary end point of the study was ORR, as defined by the proportion of patients who achieved a CR or PR. Moreover, secondary end points included duration of response (DOR), disease control rate (DCR), overall survival (OS), and safety.
After screening 238 patients, investigators enrolled 159 patients from November 29, 2017, to September 25, 2019. The median time from first dose to data cut off was 14.9 months (Interquartile range [IQR], 12.6-17.2) in the locally advanced cohort and 27.2 months (IQR, 25.6-29.2) for the recurrent/metastatic cohort. Among those in the locally advanced group, 37.0% of patients were still being treated with pembrolizumab and 63.0% had discontinued treatment. Nineteen percent of patients in the recurrent/metastatic cohort had completed treatment with pembrolizumab, while 1.9% were actively undergoing treatment and 79.0% had discontinued. Disease progression was the most common reason for treatment discontinuation across both study arms.
Additional findings from the study indicated that ORR was consistent across the subgroups included in the locally advanced cohort. Patients experienced a DCR of 64.8%. The median time to response within this group was 2.6 months and the median DOR was not reached (NR; 95% CI, NR-NR). Among those who achieved a confirmed response, 77.8% had ongoing responses as of the cut off date. It was estimated that responses at 6 months or more would be 88.1% and 84.1% at 12 months. Several patients reportedly had a reduction in tumor size 6 weeks after treatment with pembrolizumab.
Those in the recurrent/metastatic cohort had a DCR of 52.4%. Patients who received pembrolizumab as a first-line therapy (n = 14) had a median time to response of 1.4 months vs 2.1 months in the second-line setting (n = 91). Among the 95 patients with evaluable baseline and post-baseline imaging in this group, 77.9% experienced a reduction in target lesion size, with 58.9% achieving a reduction of 30% of greater. The median time to response was 1.6 months and the median DOR was NR (95% CI, 22.4-NR). Of the patients who experienced a confirmed response within the recurrent/metastatic cohort, 48.6% had ongoing responses as of the cut off date. Additionally, the estimated response at 6 months or more was thought to be 80.7% and 77.8% at 12 months.
The total patient population achieved an ORR of 40.3%, including 20 CRs and 44 PRs (95% CI, 32.6%-48.3%). The DCR in the overall population was 56.6%. In the locally advanced cohort, 44.4% of patients had developed disease progression or died. The median progression-free (PFS) survival was NR and the estimated PFS rates at 6 and 12 months were 60.9% (95% CI, 46.2%-72.8%) and 54.4% (95% CI, 39.6%-67.0%), respectively. The median OS was NR and the estimated rates at 12 and 18 months were 73.6% (95% CI, 59.5%-83.4%).
Additionally, 65.7% patients developed disease progression or died in the recurrent/metastatic cohort. The median PFS was 5.7 months (95% CI, 3.1-8.5). The median PFS was 5.7 months (95% CI, 3.1-8.5) and the estimated PFS rates at 6 and 12 months were 49.4% (95% CI, 39.3%-58.7%) and 36.4% (95% CI, 27.0%-45.9%), respectively. Moreover, the median OS was 23.8 months (95% CI, 13.4-29.8) and the OS rates at 12 and 24 months were 61.0% (95% CI, 50.9%-69.5%) and 48.4% (95% CI, 38.5%-57.6%), respectively.
In terms of safety, 2 patients in the recurrent/metastatic cohort experienced fatal treatment-related adverse effects (TRAEs), including cranial nerve disorder and immune-mediated colitis. Grade 3/4 immune-mediated AEs included severe skin reactions (n = 4), colitis (n = 2), and hepatitis (n = 2). The most common any grade TRAEs included pruritus (18.2%), fatigue (14.5%), and asthenia (12.6%). Additionally, investigators reported 1 case of grade 3 to 5 fatigue.
Hughes BGM, Munoz-Couselo E, Mortier L, et al. Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 Study): an open-label, nonrandomized, multicenter, phase 2 trial. Ann Oncol. 2021. doi:10.1016/j.annonc.2021.07.008