Skin cancers

Pembrolizumab monotherapy effective in cSCC


Pembrolizumab monotherapy has shown robust and durable antitumour activity and promising survival data in both locally advanced and recurrent/metastatic cutaneous SCC, according to an Australian oncologist.

Speaking at the American Association for Cancer Research (AACR) meeting, Dr Brett Hughes presented an interim analysis of Keynote-629 – a first analysis of the local advanced cohort and an update on an earlier analysis of the recurrent/metastatic cohort.

Keynote-629 is an international, open-label, non-randomised phase 2 study of pembrolizumab 200 mg every three weeks for up to 35 cycles. Data was collected from 59 sites across 10 countries including Australia.

The first analysis, published in JCO, demonstrated clinically meaningful and durable anti-tumour activity in recurrent/metastatic SCC with an objective response rate of 34.3%.

Dr Hughes, a medical oncologist at the Royal Brisbane and Women’s Hospital and University of Queensland, told the meeting the results in the locally advanced cohort included an overall response rate of 50.0%.

This included 16.7% of patients achieving a complete response (CR) and 33.3% achieving a partial response (PR). Of those who achieved a response, 84.1% were continuing to have a durable response for more than 12 months.

In the recurrent/metastatic cohort, the overall response rate was 35.2% with a CR of 10.5% and PR of 24.8%. Again, most responders (77.8%) were contributing to respond at more than 12 months.

He said a median PFS was estimated at 5.7 months and the overall survival “an impressive” 23.8 months in this cohort.

“Notable from the first to this interim analysis, despite similar response and disease control rate being observed, there are now more people who have achieved a complete response that have improved from a partial response,” he said.

Dr Hughes told the meeting that the findings were mostly consistent across patient subgroups by age, ECOG performance status, race, sex and geographical region.

He said pembrolizumab was generally tolerable in this elderly population >70 years, and the adverse event profile consistent with that seen in other trials.

Treatment-emergent adverse events (AEs) were reported in 69% of patients, including grade 3-5 adverse events in 11.9% of patients. Treatment discontinuations due to adverse events occurred in 8.8% of patients and two patients in the recurrent/metastatic cohort died.

Mostly mild immune-related adverse events were reported in 22.6% of patients. Those that were grade 3-5 AEs were mostly severe skin reactions in four patients, colitis in two patients and hepatitis in two patients.

Dr Hughes said the data establishes pembrolizumab as a promising treatment option for both locally advanced or recurrent/metastatic cSCC.

Commenting on the study in the AACR session, Dr Stefania Scala, from the National Cancer Institute in Naples Italy, said the results were “brilliant and exciting”.

“The second interim analysis of Keynote-629, on the clinical efficacy and safety for the locally advanced cohort and update data for the recurrent/metastatic cohort in cSCC presented solid and convincing evidence for the use of pembrolizumab …”

She said further research could focus on the role of radiotherapy in improving the immune response and targeting tumour microenvironment cells and cytochemokines to improve response and prevent resistance mechanisms.

Dr Scala noted the US FDA approved pembrolizumab for recurrent/metastatic cSCC not curable by surgery or radiation in June 2020.

Disclosures: Dr Hughes has received research support and consultant fees from MSD who funded the study. Dr Scala has no relevant disclosures.

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