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Pembrolizumab for Patients With Advanced Adrenocortical Carcinoma


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In a single-center phase II study reported in the Journal of Clinical Oncology, Raj et al found that pembrolizumab showed activity in advanced adrenocortical carcinoma.

Study Details

Thirty-nine patients with advanced adrenocortical carcinoma were enrolled in the study between February 2016 and June 2018 at Memorial Sloan Kettering Cancer Center. There was no restriction on prior therapy, and patients were treated with pembrolizumab 200 mg every 3 weeks, with treatment continuing for up to 24 months/35 cycles or until disease progression or unacceptable toxicity. Patients could continue treatment beyond progression if clinical benefit was observed. Overall, 72% of patients had received prior systemic therapy.

Responses

Median follow-up was 17.8 months (range = 5.4–34.7 months). Objective response was observed in nine patients (23%, all partial responses) and stable disease was observed in an additional seven patients (18%). Median time to response was 4.1 months. Median duration of response was not reached (lower 95% confidence interval = 4.1 months). Responses longer than 24 months on treatment were observed in three patients; these patients have had continued response off therapy. Median progression-free survival was 2.1 months, with a 6-month rate of 20%. Median overall survival was 24.9 months, with a 2-year rate of 50%.

MSI-H/MMR-D and PD-L1 Status

Of 38 tested tumors, six were microsatellite-high and/or mismatch repair deficient (MSI-H/MMR-D). Among the six patients with MSI-H/MMR-D tumors, two (both with Lynch syndrome) had objective response. The remaining seven responders had microsatellite-stable tumors; as of last analysis, responses were ongoing in six of these patients. Tumor MSI-H/MMR-D status was not a significant predictor of response (P = .61).

Among 34 tested tumors, 7 were positive for programmed cell death ligand 1 (PD-L1 > 1%). PD-L1 status was not a significant predictor of response (P = .95). Response rates were 29% in patients with PD-L1–positive tumors and 26% in those with PD-L1–negative tumors.

KEY POINTS

  • Objective response was observed in 23% of patients treated with pembrolizumab.
  • Responses were observed in both MSI-H/MMR-D and microsatellite-stable tumors.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in five patients (13%), with the most common being increased alanine transaminase/aspartate transaminase (occurring in four patients, 10%). Immune-mediated adverse events were observed in 13 patients (33%), with the most common being liver function test (LFT) elevation (23%), hypothyroidism (8%), and kidney dysfunction (5%). Among patients with immune-mediated adverse events, 10 (26%) received systemic corticosteroids, 7 (18%) had treatment interruption, and 2 (5%) discontinued treatment, both for LFT elevation. The two patients discontinuing treatment for LFT elevation have maintained responses off therapy.

The investigators concluded: “MSI-H/MMR-D tumors, for which pembrolizumab is a standard therapy, are more common in advanced adrenocortical carcinoma than has been recognized. In advanced advanced adrenocortical carcinoma that is microsatellite-stable, pembrolizumab provided clinically meaningful and durable antitumor activity with a manageable safety profile.”

Nitya Raj, MD, of the Division of Gastrointestinal Medical Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Merck & Co, Cycle for Survival, Drew O’Donoghue Fund, and National Cancer Institute. For full disclosures, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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