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Post-hoc analysis supports pembrolizumab’s benefit in recurrent head, neck squamous cell carcinoma

Issue: November 10, 2018

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MUNICH — A post-hoc analysis of the randomized phase 3 KEYNOTE-040 trial presented at European Society for Medical Oncology Congress showed a trend toward improved OS with pembrolizumab compared with three other standard treatments for recurrent head and neck squamous cell carcinoma.

Researchers also reported improved second PFS (PFS2) — defined as the time from randomization to disease progression after initiation of a new anticancer therapy — among pembrolizumab-treated patients.

“The topline results of the KEYNOTE-040 trial demonstrated a clear benefit of pembrolizumab, as well as an additional demonstration of benefit in OS and response rates,” researcher Ezra E.W. Cohen, MD, associate director of Moores Cancer Center at UC San Diego, told HemOnc Today. “What this current evaluation shows, interestingly enough, is that patients treated with pembrolizumab seem to derive an even greater benefit with subsequent therapy.

“This benefit appeared better in the pembrolizumab arm than the standard treatment arm — even among those who received [prior] immunotherapy — suggesting that sequencing may be very important, and that there is a continued effect of the anti-PD-1 antibodies on the T-cell stimulation that carries forward to the subsequent lines of therapy.”

The multicenter, open-label KEYNOTE-040 trial compared the anti-PD-1 monoclonal antibody pembrolizumab (Keytruda, Merck) with standard of care for patients with recurrent or metastatic HNSCC.

Researchers randomly assigned 495 patients 1:1 to pembrolizumab 200 mg every 3 weeks for 24 months, or investigator’s choice of 40 mg/m² weekly methotrexate, 75 mg/m² docetaxel every 3 weeks, or the EGFR inhibitor cetuximab (Erbitux, Eli Lilly) administered as a 400 mg/m² loading dose and then 250 mg/m² weekly.

OS in the intention-to-treat population served as the primary endpoint.

Previously released results showed pembrolizumab significantly extended OS compared with investigator’s choice (median 8.4 months vs. 6.9 months; HR = 0.8; 95% CI, 0.65-0.98).

In the post hoc analysis, Cohen and colleagues — including Christophe Le Tourneau, MD, oncologist in the department of medical oncology at Institute Curie in Paris — compared OS and PFS between patients assigned pembrolizumab and each of the three investigator-chosen therapies. They also assessed PFS2 and outcomes based on whether patients received prior cetuximab treatment.

The results showed a trend toward longer median OS with pembrolizumab (8.4 months) than with methotrexate (6 months; HR for pembrolizumab = 0.81; 95% CI, 0.59-1.11), cetuximab (7.1 months; HR for pembrolizumab = 0.77; 95% Ci, 0.57-1.03) and docetaxel (7.7 months; HR for pembrolizumab = 0.81; 95% CI, 0.62-1.05).

Among patients who had no prior cetuximab exposure (n = 210), pembrolizumab-treated patients achieved longer median OS (8.2 months vs. 6.9 months; HR = 0.78; 95% CI, 0.56-1.07), longer median PFS (2.9 months vs. 2.3 months; HR = 0.84; 95% CI, 0.62-1.15), and higher ORR (21.6% vs. 13%). However, the differences did not reach statistical significance.

Among patients previously treated with cetuximab (n = 285), pembrolizumab-treated patients achieved longer median OS (8.4 months vs. 7.1 months; HR = 0.89; 95% CI, 0.68-1.16) but shorter median PFS (2.1 months vs. 2.3 months; HR = 1.13; 95% CI, 0.88-1.46). The overall response rate was higher among pembrolizumab-treated patients (9.7% vs. 7.9%) but the difference did not reach statistical significance.

In the entire cohort, median PFS2 was longer for pembrolizumab-treated patients (6.6 months vs. 5.4 months; HR = 0.75; 95% CI, 0.62-0.91).

“These data are very interesting from a mechanistic perspective and very encouraging for our patients,” Cohen said.

Researchers intend to conduct future analyses that will evaluate subsequent therapies after initial progression. – by Jennifer Southall

Reference:

Le Tourneau CL, et al. Abstract 1047_PD. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosures: Merck provided funding for this study. Cohen reports consultant/advisory roles with AstraZeneca, Bristol-Myers Squibb, EMD Serono, Human Longevity Inc., Merck and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.