Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma

Abstract

BackgroundBasal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.MethodsWe conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0.ResultsA total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate.ConclusionsThe clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.

Reinduction of Hedgehog Inhibitors after Checkpoint Inhibition in Advanced Basal Cell Carcinoma: A Series of 12 Patients

“…Whilst only one patient responded to the second-line PD1i, a mixed pattern of response was noted for HHI reinduction ranging from CR to PD as best response. Response rate to second-line PD1i treatment in our limited patient cohort was lower than previously reported (24–31% [ 6 , 7 , 8 ]). This might be due to a selection bias, since only patients with subsequent HHI reinduction were included.…”

“…When first-line therapy with HHIs fails, consecutive PD1i is approved as second-line treatment. However, response rates for cemiplimab after HHI therapy are reported at only 24–31%, or stable disease control remains only temporary [ 6 , 7 , 8 , 9 ].…”

“…It has been found that 31% of patients with laBCC and 24% with mBCC will respond to second-line treatment with cemiplimab after HHI. Even though PD1i pembrolizumab is at present not approved for treatment of aBCC, small studies and case series suggest a similar response rate in aBCC pretreated with HHI compared to cemiplimab [ 5 , 6 , 7 , 8 ].…”

Efficacy and limitations of pembrolizumab for lung cancer and Hodgkin lymphoma

“…Among all 29 patients, disease control rate (DCR) was 62%. These data display a comparable therapeutic efficacy [2].…”

“…ORRs of three cohorts were all 69% while CR rate was 22.4%. Separately, ORR was 73.9%, 64.2%, and 70% in three cohorts (1,2,3), respectively. The result indicates a favorable efficacy of pembrolizumab administration against cHL, and no impact of ASCT on pembrolizumab efficacy was reported.…”