Pembrolizumab effective in R/M cutaneous squamous cell carcinoma

Pembrolizumab has demonstrated efficacy and acceptable safety in patients with recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC) in the single-arm phase II KEYNOTE-629 trial, leading to US FDA approval for its use in patients with R/M cSCC not curable by surgery or radiation therapy.

KEYNOTE-629 represents the largest clinical trial to date in patients with R/M cSCC. A total of 105 patients (median age, 72 years; male, 76.2 percent) were treated with pembrolizumab 200 mg every 3 weeks and followed up for a median of 11.4 months. [J Clin Oncol 2020, doi: 10.1200/JCO.19.03054]

At the first interim analysis, the primary endpoint of objective response rate (ORR) was 34.3 percent (n=36), with 3.8 percent of patients (n=4) achieving complete response (CR) and 30.5 percent (n=32) achieving partial response (PR). Stable disease was reported in 29.5 percent of patients (n=31), and the disease control rate was 52.4 percent (n=55).

The median time to response was 1.5 months, and median duration of response was not reached (NR).

Among the 36 responders, 25 patients were estimated to have ongoing responses at ≥6 months, while one patient was estimated to have ongoing response at ≥12 months. “Patients experienced rapid tumour reduction after 6 weeks of pembrolizumab treatment,” the investigators noted.

Median progression-free survival (PFS) was 6.9 months, while median overall survival (OS) was NR at the first interim analysis.

In subgroup analysis, ORR was 50 percent (CR, n=2; PR, n=5) in 14 patients receiving pembrolizumab as first-line therapy, who were enrolled after protocol amendment. These patients had a shorter follow-up duration of 9.2 months, and their median PFS and OS was 8.3 months and NR, respectively. Their PFS rates at 6 months and 12 months were 70.7 percent and NR, respectively, while 6-month and 12-month OS rates were 78.6 percent and NR, respectively.

Among 91 patients who received pembrolizumab as second-line or later-line treatment, who were followed up for a median of 12.1 months, ORR was 31.9 percent (CR, n=2; PR, n=27). Median PFS was 5.4 months, while 6-month and 12-month PFS rates were 47.3 percent and 32.2 percent, respectively. Median OS was NR, while OS rates at 6 months and 12 months were 79.1 percent and 61.3 percent, respectively.

In 47 patients with tumours located primarily in the head and neck, which have been recognized as more aggressive and difficult to treat than cSCC in other locations, ORR was 42.6 percent (CR, n=1; PR, n=19), median PFS was 8.5 months, and median OS was NR. Among 58 patients with tumours in other primary locations, ORR was 27.6 percent (CR, n=2; PR, n=21), median PFS was 4.2 months, and median OS was 10.3 months.

“Biomarker subgroup analysis showed pembrolizumab treatment benefit regardless of PD-L1 expression,” the investigators wrote. 

The most common treatment-related adverse events (TRAEs) were pruritis (14.3 percent), asthenia (13.3 percent), and fatigue (12.4 percent). Grade 3–5 TRAEs occurred in 5.7 percent of patients, with one death due to treatment-related cranial nerve neuropathy.

“Pembrolizumab demonstrated comparable responses and similar or favourable safety compared with historical data on systemic therapies in R/M cSCC,” the investigators noted. “The ORR of pembrolizumab exceed that of cetuximab or panitumumab.” [Cancer 1985;55:1629-1632; Cancer 1991;67:2030-2032; J Clin Oncol 2011;29:3419-3426; Ann Oncol 2014;25:2047-2052]

The responses to pembrolizumab were clinically meaningful and durable, with acceptable safety, in a study population comprising primarily elderly R/M cSCC patients, which supports its use in clinical practice, the investigators concluded.