Pembrolizumab also appears to garner modest anti-tumor activity regardless of PD-L1 expression in patients with advanced thyroid cancer.
Treatment with pembrolizumab (Keytruda) monotherapy elicited long-lasting anti-tumor activity in a small group of patients with advanced thyroid carcinoma, according to results from cohort 1 of the phase 2 KEYNOTE-158 study (NCT02628067).
In the overall cohort (n = 103), the objective response rate (ORR) was 6.8% (95% CI, 2.8%-13.5%). Among 7 patients with an objective response, 2 had a complete response (CR), and 5 had a partial response (PR). The median time to response was 2.1 months (range, 1.3-10.3), and the median duration of response (DOR) was 18.4 months (range, 4.2-47.2).
Additionally, the disease control rate was 67.0%.
The ORR was 8.7% (95% CI, 2.4%-20.8%) for patients with PD-L1–positive disease (n = 46), including 2 patients with a CR and 2 others with a PR. The ORR was 5.7% (95% CI, 1.2%-15.7%) for those with PD-L1–negative disease (n = 53), which included 3 PRs. The disease control rate for the PD-L1–positive and PD-L1–negative populations, respectively, was 67.4% and 64.2%.
“Among the small group of patients who experienced a response, those responses were durable, and the safety profile was consistent with what was previously reported with pembrolizumab,” the study authors stated. “Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents to achieve higher response rates than observed in this study.”
Investigators of the ongoing, single-arm, multi-center, multi-cohort, open-label phase 2 KEYNOTE-158 study evaluated pembrolizumab in a cohort of patients with advanced thyroid carcinoma. Patients received 200 mg of pembrolizumab as a 30-minute intravenous infusion once every 3 weeks for 35 cycles or until disease progression.
The primary end point was ORR based on independent central radiologic review and RECIST v1.1 guidelines. Secondary end points included DOR, progression-free survival (PFS), overall survival (OS), safety, and tolerability.
For subgroup analyses, investigators determined PD-L1 tumor statuses using the IHC 22C3 pharmDx assay. Investigators defined tumors with a combined positive score (CPS) of at least 1 as PD-L1 positive, while tumors with a CPS less than 1 were PD-L1 negative.
Patients 18 years or older with histologically or cytologically confirmed thyroid carcinoma that had progressed on at least 1 prior line of standard therapy for metastatic or unresectable disease were eligible for enrollment. Additional inclusion criteria included having measurable disease per RECIST v1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; and adequate hematologic, renal, hepatic, and coagulation function.
Investigators enrolled a total of 103 patients across 43 sites in 18 countries befromtween February 15, 2016 to January 11, 2017. Additionally, 84.5% (n = 87/103) patients discontinued treatment. Reasons for treatment discontinuation included disease progression (65.0%), adverse effects (AEs; 11.7%), patient withdrawal (5.8%), physician decision (1.0%), and loss to follow-up (1.0%).
The median patient age was 62.0 years (range, 27-85), and 98.1% of patients had stage IV disease. Additionally, most patients received at least 2 prior lines of systemic therapy (62.1%) and prior radiation therapy (53.4%). Most patients also had PD-L1 negative tumors (51.5%).
In total, 93.2% of patients had a PFS event by the time of data cut-off. Median PFS was 4.2 months (95% CI, 3.9-6.2) in the overall population. Additionally, the estimated PFS rate was 47.1% at 6 months, 28.0% at 12 months, and 6.8% at 24 months.
Overall, 55.3% of patients died. Investigators reported a median OS of 34.5 months (95% CI, 21.2-not reached). Estimated OS rates were 81.6% at 12 months, 59.0% at 24 months, 48.2% at 36 months, and 45.9% at 48 months.
Investigators observed treatment-related AEs (TRAEs) in 69.9% of patients, which included fatigue (19.4%), pruritus (14.6%), and rash (14.6%). Additionally, 12.6% of patients had at least 1 grade 3/4 TRAE.
Overall, 9.7% of patients discontinued treatment with pembrolizumab following TRAEs. Additionally, there were 2 patients who died due to grade 5 TRAEs: arterial hemorrhage and malignant neoplasm progression.
Oh D, Algazi A, Capdevila J, et al. Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Cancer. Published online February 7, 2023. doi:10.1002/cncr.34657