Pembrolizumab (Keytruda) demonstrated promising antitumor activity with durable responses in patients with advanced thyroid cancer, according to results from the KEYNOTE-028 trial presented at the 2016 ASCO Annual Meeting.
The overall response rate (ORR) with the PD-1 inhibitor was 9.1%, which included 2 partial responses (PR).
“It’s not quite as robust as this agent has been in some of the other cancers, but it suggests that there is activity there,” study author Marcia S. Brose, MD, PhD, an associate professor of Otorhinolaryngology, Head and Neck Surgery, at the Hospital of the University of Pennsylvania, said in an interview with
The nonrandomized phase Ib KEYNOTE-028 trial examined pembrolizumab in 20 different solid tumor types. The results presented at ASCO were from a cohort of 22 patients with advanced thyroid cancer, which consisted of 15 patients (68.2%) with papillary carcinoma and 7 patients (31.8%) with follicular carcinoma.
The median patient age was 60 years (range, 23-76) and approximately 60% of the patients were female. Fourteen patients were white, 7 were Asian, and 1 was multiracial. The ECOG performance status was 1 for 8 patients (36.4%), 0 for 11 patients (50%), and unknown for the remaining 3 patients (13.6%).
Patients had to have failed on or been ineligible to receive standard-of-care treatment. Those who had received therapy for advanced disease had been treated with 1 (n = 7; 31.8%), 2 (n = 5; 22.7%), 3 (n = 3; 13.6%), or 4 (n = 1; 4.5%) prior lines therapy. Eighteen patients (81.8%) were iodine refractory, 7 (31.8%) had prior sorafenib (Nexavar), and 1 (4.5%) had prior lenvatinib (Lenvima).
The cohort included only PD-L1–positive patients, which the protocol defined as PD-L1 expression on ≥1% of tumor cells, as determined by IHC. PD-L1 expression was measured at a central laboratory in archival tissue or a newly obtained core excision biopsy.
Patients received pembrolizumab every 2 weeks for a maximum of 2 years or until disease progression, unacceptable toxicity, or withdrawn consent. For the first 6 months, responses were assessed every 8 weeks, and then every 12 weeks thereafter. Those patients with radiographic progression who remained clinically stable were allowed to continue receiving pembrolizumab until the progression was confirmed by follow-up imaging ≤4 weeks later.
ORR by investigator review was the the primary endpoint. Secondary outcome measures included duration of response, progression-free survival (PFS), and overall survival (OS).
As of February 17, 2016, the median follow-up duration was 82.6 weeks (range 29.4-96.9 weeks). The ORR was 9.1% (95 CI, 1.1-29.2), consisting of 2 PRs. There was an additional patient who achieved an unconfirmed PR.
Both patients with a PR had papillary thyroid cancer. The response occurred at week 16 in 1 patient and week 24 in the other. One of the confirmed PRs was ongoing at the data cutoff, and 4 patients were still receiving treatment.
At the data cutoff, the median duration of response had not yet been reached (range, 36.7-55.9+ weeks) and the stable disease rate was 54.5% (n = 12; 95% CI, 32.2-75.6). Eight patients (36.4%; 95% CI 17.2-59.3) had progressive disease.
The median PFS was 6.8 months (95% CI, 1.9-14.1). The 6-month PFS rate was 58.7% and the 12-month PFS rate was 36%. Median OS had not yet been reached (95% CI, 18.6 months to not reached). The 6- and 12-month OS rates were 100% and 89.9%, respectively.
Adverse events (AEs) were evaluated throughout the study and for 30 days after its completion (90 days for immune-related AEs of clinical interest). Pembrolizumab was well tolerated with a safety profile comparable to previously reported outcomes with the PD-1 inhibitor.
Eighteen of the 22 patients (81.8%) experienced at least 1 treatment-related AE. The most common all-grade AEs were diarrhea (n = 7), fatigue (n = 4), pruritus (n = 3), rash (n = 3), decreased appetite (n = 2), headache (n = 2), cough (n = 2), and pneumonitis (n = 2). The 1 grade ≥3 AE was grade 3 colitis. There were no patient deaths or discontinuations due to treatment with pembrolizumab.
The use of single-agent pembrolizumab in advanced thyroid cancer is being further explored in the KEYNOTE-158 trial (NCT02628067). The multicohort phase II study, which is investigating a flat dose of pembrolizumab (200 mg once every 3 weeks), is currently enrolling patients.
According to Brose, combination studies with pembrolizumab in thyroid cancer are also being launched.
“There is going to be a follow-up study of pembrolizumab in conjunction with lenvatinib moving forward, so there is an interest in trying to enhance the data. [Pembrolizumab] shows activity and it shows that there might be a role for it in thyroid cancer. However, we need to do more studies and combinations might be the way to go.”
Mehnert JM, Varga A, Marcia Brose M, et al. Pembrolizumab for advanced papillary or follicular thyroid cancer: preliminary results from the phase 1b KEYNOTE-028 study. J Clin Oncol 34, 2016 (suppl; abstr 6091).