The following article features coverage from the 2020 Gastrointestinal Cancers Symposium meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Pembrolizumab, an inhibitor of programmed death 1 receptor (PD-1), demonstrated clinical activity in subgroups of patients with pretreated anal squamous cell carcinoma (ASCC) characterized by high and low levels of programmed death ligand 1 (PD-L1) tumor expression, according to results of a study reported at the 2020 Gastrointestinal Cancers Symposium in San Francisco, California.

There are limited treatment options for patients with advanced ASCC that has progressed following frontline therapy. Building on the results of the multicohort phase 1b KEYNOTE-028 trial, which demonstrated the antitumor activity of pembrolizumab in patients with heavily pretreated PD-L1–positive advanced or recurrent cancers (including ASCC), the phase 2 KEYNOTE-158 trial ( Identifier: NCT02628067) was designed to further explore the safety and efficacy of pembrolizumab in pretreated adults with advanced solid tumors.

The primary study endpoint of this open-label, multicohort, single-arm phase 2 clinical trial was objective response rate (ORR), with secondary study endpoints of duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety. Study enrollment was not limited by the level of tumor PD-L1 expression.

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The majority of the 112 patients with metastatic and/or unresectable ASCC enrolled in the study were women (81.3%), and approximately three-quarters of all participants had received at least 2 prior therapies. The median patient age was 61 years. 

At a median follow-up of 12 months, the ORR was 11.6%, with 5 and 8 patients achieving a complete response and a partial response, respectively; median DOR had not yet been reached at the time of study presentation.

When ORR was determined according to the level of tumor PD-L1 expression, 14.7% of patients with a PD-L1 combined positive score (CPS) of 1 or higher and 6.7% of those with a PD-L1 CPS of less than 1 achieved a response.

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The median PFS and median OS for all patients with advanced ASCC was 2 months (95% CI, 2.0–2.1) and 12 months (95% CI, 9.1–15.4), respectively.

With respect to the safety of pembrolizumab in this patient cohort, grade 3 to grade 5 adverse events (AEs) were reported in 18.8% of patients, but no treatment-related deaths occurred. Although approximately one-quarter of patients experienced immune-mediated AEs/infusion, only 4 patients (3.6%) discontinued pembrolizumab due to treatment-related AEs. 

In summary, the study authors wrote that “pembrolizumab demonstrated antitumor activity and manageable toxicity in patients with heavily pretreated advanced ASCC, regardless of PD-L1 status.”

Disclosure: This study was sponsored by Merck Sharp & Dohme Corp. Some of the authors reported financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the study abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO GI annual meeting by visiting the conference page.


  1. Marabelle A, Cassier PA, Fakih M, et al.  Pembrolizumab for advanced anal squamous cell carcinoma (ASCC): Results from the multicohort, phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(suppl 4):Abstract 1.
  2. Ott PA, Piha-Paul SA,  Munster P, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017;28(5):1036-1041.