KEYNOTE-158: pembrolizumab in previously treated advanced cervical cancer

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By: Stijn van den Borne, MSc | Last updated: 24 April 2019 | In: Gynaecological Cancer, Haematology, Oncology, Chemotherapy, Immunotherapy

Article Keywords

PD-1, PD-L1, pembrolizumab, Merck, Keytruda, cervical cancer, chemotherapy

Immunotherapy with programmed death 1 (PD-1) antibody pembrolizumab led to an objective response rate (ORR) of 14.6% in previously treated advanced cervical cancer patients with PD-L1–positive disease, as reported by Chung et al. on behalf of the KEYNOTE-158 investigators in the Journal of Clinical Oncology.¹

“Pembrolizumab monotherapy demonstrated durable antitumor activity and manageable safety in patients with advanced cervical cancer. On the basis of these results, the U.S. Food and Drug Administration granted accelerated approval of pembrolizumab for patients with advanced PD-L1–positive cervical cancer who experienced progression during or after chemotherapy.”

KEYNOTE-158

The recent publication in the Journal of Clinical Oncology reported on a cohort of 98 adult patients with previously treated advanced cervical cancer of phase II KEYNOTE-158 (NCT02628067) basket trial in multiple types of solid tumours. Eligible patients in the cervical cancer cohort were ≥ 18 years old with histologically or cytologically confirmed advanced cervical cancer and measurable disease by RECIST v1.1, had progression to or intolerance for one or more lines of standard therapy, had an ECOG performance status of 0 or 1, and had an adequate organ function. All patients received 200 mg pembrolizumab every 3 weeks for up to 2 years or until progression disease or the occurrence of intolerable toxicity. The primary efficacy endpoint was the ORR per independent central radiologic review (RECIST v1.1). Tumour imaging in the first year was performed every 9 weeks, and every 12 weeks in the second year of treatment.

Results

Median follow-up was 10.2 months. Among the 98 recruited cervical cancer patients (median age: 46 years), 82 patients (83.7%) had PD-L1–positive tumours (combined positive score [CPS] ≥1). Within this PD-L1–positive group, 77 patients (94%) had received ≥1 line of standard chemotherapy for recurrent or metastatic disease prior to study enrolment. The ORR in the overall cervical cancer study population was 12.2% (12 out of 98), including 3 complete responses. Notably, responses were limited to the 82 patients with PD-L1–positive disease, resulting in an ORR in the PD-L1–positive group of 14.6% (12 out of 82), with a median time to response of 2.1 months. The median duration of response was not yet reached (range: ≥3.7 to ≥ 18.6 months); seven patients had a response lasting ≥12 months at the time of analysis. Looking at the group of 77 patients receiving ≥1 line of chemotherapy for recurrent or metastatic disease prior to enrolment showed that 11 patients (14.3%) in this group had a response to the PD-1 inhibitor. Finally, the median progression-free survival and median overall survival measured 2.1 months and 9.4 months in the overall population and 2.1 months and 11.0 months in the PD-L1–positive subgroup, both respectively.

Safety

Any-grade treatment-related adverse events (TRAEs) occurred in 65.3% of patients, the most common being hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%). Grade 3 or 4 TRAEs occurred in 12.2% of patients, the most common being increased alanine transaminase (3.1%). Finally, TRAEs leading to discontinuation of treatment occurred in 4 patients (4.1%). In total 25.5% of patients experienced immune-mediated adverse events (irAEs). Grade 3 or 4 irAEs occurred in 5.1% of patients and included hepatitis (2 patients), severe skin reactions (2 patients), and adrenal insufficiency (1 patient). Common irAEs of any grade included hypothyroidism (11.2%) and hyperthyroidism (9.2%). No treatment-related deaths were reported.

References

Chung HC, et al. J Clin Oncol. 2019. doi: 10.1200/JCO.18.01265.

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Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).