Real-World Analysis Explores Clinical Activity, Safety of PD-1 Inhibition in Advanced BCC

Locally advanced or metastatic basal cell carcinoma can be challenging to treat, but programmed death receptor 1 inhibition may hold potential as a tolerable, effective approach in patients of all ages.

Advanced or metastatic basal cell carcinoma (BCC) currently has few treatment options, but programmed death receptor 1 (PD-1) inhibition has emerged as a potentially effective therapy in a subset of BCC patients. A study published in the Journal for Immunotherapy of Cancer found that real-world patients with advanced or metastatic BCC treated with PD-1 inhibitors had similar clinical results to those seen in trials, supporting the inclusion of PD-1 inhibition in treatment regimens for patients with unresectable or metastatic disease.

More than 2 million cases of BCC are diagnosed annually in the United States, making it the most common type of cancer in the US population—but locally advanced and metastatic cases are rare. Patients with small, localized lesions typically have good long-term outcomes with several treatment options, including minimally invasive surgery. Patients with BCC that is recurrent, involves metastases, or is locally advanced are faced with fewer treatment options and no standard clinical management guidelines due to its rarity.

Inhibition of the Hedgehog pathway, which is upregulated in patients with BCC, is an established first-line therapy option for advanced or metastatic BCC but is limited by high toxicity and low tolerability. Considering the dose interruptions and treatment modifications often resulting from Hedgehog pathway inhibitors (HHIs), more salvage therapy options for patients who are not successful with HHI are necessary.

PD-1 inhibition is effective in several cancer types, including cutaneous cancers, and the PD-1 inhibitor cemiplimab is approved for patients who have already received an HHI. With positive and durable responses, better overall survival (OS), and less toxicity than many other systemic agents, PD-1 inhibitors hold potential even for frail or older patients with advanced BCC. The current study aimed to provide real-world insight into the efficacy, safety, and outcomes of PD-1 inhibitor therapy in patients with BCC.

The multicenter, retrospective study included 20 patients with locally advanced BCC and 9 patients with metastatic BCC. The median patient age was 70 years—58.6% were 70 or older, and 27.6% were 75 or older. A total of 19 patients had aggressive subtypes, including basosquamous, morpheaform, and micronodular malignancies.

In the overall cohort, 72.4% of patients underwent surgery for BCC previously, 62.1% received prior radiation, and 82.8% of patients received HHIs prior to PD-1 inhibition. Of the patients who received HHIs, 75% experienced disease progression and discontinued HHI therapy.

At a median 11-month follow-up, 11 patients had died, 17 were alive with at least 3 months of follow-up, and 1 was lost to follow-up. The median number of PD-1 treatment cycles was 6, and median therapy duration was 4.8 months. The PD-1 inhibitors pembrolizumab, cemiplimab, and nivolumab were all used in 58.6%, 31.0%, and 10.3% of patients, respectively.

A total of 5 patients achieved partial response, and 4 achieved complete response. Two patients initially had stable disease and eventually achieved either partial or complete responses. Overall, the objective response rate (ORR) was 31%. A subset analysis showed a 35% ORR for patients with locally advanced disease and 22.2% for patients with metastatic disease.

Median duration of response was not reached, but the estimated median progression-free survival (PFS) and OS were 12.2 months 32.4 months, respectively. PFS or OS were not associated with any clinical or pathological variables. A total of 19 patients developed toxicity of any grade, while 2 patients developed grade 3 or higher toxicities. There were no fatal adverse events, and age did not seem to affect rates of adverse events. Four patients (13.8%) in total discontinued PD-1 inhibition due to toxicity.

Despite a limited sample size, single-center design, and lack of biomarkers, these findings are in line with those of pivotal clinical trials of PD-1 inhibition in locally advanced BCC patients. Ongoing studies are exploring PD-1 inhibition in the neoadjuvant and adjuvant setting for patients who have complex resections or surgical morbidity, as well as in combination with HHI in the unresectable or metastatic settings.

“Going forward, future efforts should be pursued to better elucidate the role of PD-1 therapy in BCC,” the authors wrote. “As PD-1 inhibition can lead to durable responses via activation of the antitumor immune response, and also is generally well tolerated, even among older patients, it would be worthwhile to understand how this approach can be combined with others.”


In GK, Nallagangula A, Choi JS, et al. Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma. J Immunother Cancer. Published online May 11, 2022. doi:10.1136/jitc-2022-004839