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AACR 2019: Data Analysis Shows Activity of Pembrolizumab in Pretreated Patients With Advanced Small Cell Lung Cancer

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Key Points

  • An analysis of pooled data from the phase Ib KEYNOTE-028 trial and the phase II KEYNOTE-158 study found that pembrolizumab provided antitumor activity with durable responses in pretreated patients with advanced small cell lung cancer.
  • According to the analysis, 9 of the 16 responders to pembrolizumab monotherapy achieved responses lasting at least 18 months, and there were no unexpected toxicities.

The results of an analysis of pooled data from the phase Ib KEYNOTE-028 trial and the phase II KEYNOTE-158 study of the anti–programmed cell death protein 1 monoclonal antibody pembrolizumab in the treatment of advanced small cell lung cancer has found that the therapy provided antitumor activity with durable responses in pretreated patients with the cancer. In the analysis, 9 of 16 responders to the therapy achieved responses lasting at least 18 months, and there were no unexpected toxicities from pembrolizumab. The study was presented by Chung et al at the American Association for Cancer Research (AACR) Annual Meeting (Abstract CT073).

According to the American Cancer Society, lung cancer is the most common cancer in men and women in the United States, with about 228,000 new cases diagnosed each year. It is also the most deadly cancer, with nearly 143,000 deaths expected this year. Small cell lung cancer comprises about 15% of diagnosed lung cancers, and although smoking is strongly associated with the development of lung cancer, it is especially linked to small cell lung cancer. About 70% of patients with small cell lung cancer have advanced disease at diagnosis, with less than 2% of patients still alive 5 years after diagnosis.

Study Methodology

Of the 131 patients with small cell lung cancer enrolled in the two trials, 83 were eligible for analysis. The median age was 62, 64% of patients were men, and 36% had received ≥ 3 lines of systemic therapy.

Patients from KEYNOTE-028 were required to have programmed cell death ligand 1 (PD-L1)-positive tumors, and patients in the KEYNOTE-158 study were not. The primary endpoint in both studies was objective response rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

Duration of response, progression-free survival, and overall survival were secondary endpoints, estimated using the Kaplan-Meier method. For this analysis, assessment of response was by independent central review. As of the data cutoff date, the median follow-up was 7.7 months.

Study Results

The researchers found the objective response rate was 19.3% (95% confidence interval [CI] = 11.4%–29.4%). Two patients had a complete response and 14 had a partial response per independent central review; 14 of 16 responders were PD-L1–positive. The median duration of response was not reached (range = 4.1–35.8 [ongoing] months).

Nine of the 16 responders (61% per Kaplan-Meier estimate) had responses lasting ≥ 18 months. The median progression-free survival was 2.0 months (95% CI = 1.9–3.4 months) and median overall survival was 7.7 months (95% CI = 5.2–10.1 months). Twelve- and 24-month rates were 16.9% and 13.1% for progression-free survival, and 34% and 21% for overall survival.

Among all patients with small cell lung cancer in KEYNOTE-028 and KEYNOTE-158, 8% had a grade 3 treatment-related adverse event (no grade 4 treatment-related adverse events). Three patients had grade 5 treatment-related adverse events (intestinal ischemia, pneumonia, encephalopathy), and 21% experienced an immune-mediated adverse event or infusion reaction.

Clinical Significance

“Our findings are particularly noteworthy given that data show that historically patients with small cell lung cancer in the third-line treatment setting have limited survival benefit, with a duration of response of less than 2 months and median survival of around 2 to 3 months,” said Hyun Cheol Chung, MD, PhD, Professor of Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Republic of Korea, and lead author of the study. “Our study shows that pembrolizumab monotherapy can provide durable clinical benefit with manageable toxicity in this hard-to-treat patient population.”

Disclosure: Funding for this research was provided by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co. The study authors’ full disclosures can be found at abstractsonline.com.

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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