FDA Expands Label for Pembrolizumab to Include Treatment of Locally Advanced cSCC

The FDA has expanded its approval for pembrolizumab (Keytruda) monotherapy to include the treatment of patients with locally advanced cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation, according to a press release from Merck.¹

The new indication comes after approval was granted to pembrolizumab as monotherapy for the treatment of patients with recurrent or metastatic disease that is not curable by surgery or radiation in June 2020. Results from the interim analysis of the phase 2 open-label, single-arm KEYNOTE-629 trial (NCT03284424) support the expanded indication.

“This approval is great news for these patients and further demonstrates Merck’s commitment to the skin cancer community. Keytruda has shown meaningful efficacy in patients with locally advanced or recurrent or metastatic cutaneous squamous cell carcinoma that cannot be cured by surgery or radiation,” said Vicki Goodman, MD, vice president, clinical research, Merck Research Laboratories. “This expanded indication reinforces the role of Keytruda in this cancer type, which is the second most common form of non-melanoma skin cancer.”

KEYNOTE-629 enrolled 159 patients enrolled in the study, 54 with locally advanced cSCC were treated with pembrolizumab 200 mg via intravenous infusion on day 1 of each 3-week cycle for about 2 years.

The study explored 2 cohorts of patients. In 1 cohort, patients had recurrent or metastatic disease that is not curable by surgery or radiation, and in the other, patients had locally advanced cSCC.

The primary end point of the study was objective response rate (ORR), and the secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), the incidence of adverse events (AEs), and the number of patients who discontinued treatment due to AEs.

The locally advanced cSCC population were a median age of 76 years (range, 35-95), with 80% being 65 years or older. The population was also 72% male, 83% White, and 41% had an ECOG performance status of 0 and 59% with an ECOG performance status of 1. One or more prior lines of therapy were received in 22% of patients, and 63% received prior radiation therapy.

Interim results showed that patients in the pembrolizumab arm achieved an ORR of 50% (95% CI, 36%-64%). Of the responses observed with the monotherapy, 17% were complete responses and 33% were partial responses. The DOR was 6 months or longer for 81% of the study population, and 12 months or longer for 37%.

The interim analysis for the recurrent or metastatic disease cohort, which was published in the Journal of Clinical Oncology, showed an ORR of 34.3% (95% CI, 25.3%-44.2%) in 105 patients. Responses included CRs in 4 patients and PRs in 34 patients for a DCR of 2.4% (95% CI, 42.4%-62.2%). In this cohort, the median DOR was not reached (range, 2.7 to 13.1+).²

Survival data from the recurrent or metastatic group were available. The median PFS was 6.9 months (95% CI, 3.1-8.5), and the median OS was not reached (95% CI, 10.7 to not reached).

In terms of safety, treatment-related AEs were seen in 66.7% of the recurrent or metastatic cohort. The most common AEs observed were pruritus (14.3%), asthenia (13.3%), and fatigue (12.4%). Grade 3 to 5 treatment-related AEs occurred in 5.7% of the patients.

In relation to the locally advanced cSCC cohort, the median duration of exposure to pembrolizumab was 6.9 months (range, 1 day to 28.9 months). The AEs observed in the cohort were similar to those seen in other cohorts. Of the grade 3 or 4 laboratory abnormalities that occurred, there was a higher incidence of lymphopenia (10%) and decreased sodium (10%) among patients with locally advanced cSCC.¹

The label for pembrolizumab warns about immune-mediated AEs, which can present any time during or after treatment. The AEs may include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. It is important for physicians to identify the AEs early and begin to manage them. In some cases, pembrolizumab should be withheld or permanently discontinued with corticosteroids administered, if appropriate.

_References:

_{FDA approves expanded indication for merck’s Keytruda® (pembrolizumab) in locally advanced cutaneous squamous cell carcinoma (cSCC). News release. July 6, 2021. Accessed July 6, 2021 https://bit.ly/3wiArgD}

_{Grob J, Gonzalez R, Basset-Seguin N, et al. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: a single-arm phase ii trial (KEYNOTE-629). J Clin Oncol. 2020;38(25): 2916-2925. doi: 10.1200/JCO.19.03054.}