Durable Responses Reported With Pembrolizumab in Heavily Pretreated Extensive-Stage Small Cell Lung Cancer



The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab (Keytruda) has shown durable antitumor activity in patients with extensive-stage small cell lung cancer (SCLC) that expresses programmed cell death ligand 1 (PD-L1), according to an update of the KEYNOTE-028 trial.1

Patrick A. Ott, MD, PhD

Patrick A. Ott, MD, PhD

“Median overall survival for extensive-stage small cell lung cancer is 8 to 12 months, and no therapy has improved on the 15% to 20% response rate and 30% 1-year overall survival provided by second-line topotecan,” commented lead investigator Patrick A. Ott, MD, PhD, a medical oncologist and Clinical Director of the Center for Immuno-Oncology at the Dana-Farber Cancer Institute in Boston.

However, the trial’s updated data showed that after a median follow-up of 9.8 months, 33.3% of patients had a complete or partial response to pembrolizumab, with responses lasting for a median of 19.4 months. Additionally, the 1-year rate of overall survival with the immune checkpoint inhibitor approached 40%, and the favorable safety profile seen initially was unchanged

“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1–positive small cell lung cancer. Responses were durable,” Dr. Ott concluded. “The safety profile was consistent with the prior experience [in other tumor types], and it was identical with longer follow-up.”

Ongoing trials of pembrolizumab for extensive-stage SCLC—one looking at maintenance after combination chemotherapy (NCT02359019) and another looking at its combination with chemotherapy in the first-line setting (NCT02580994, REACTION trial)—should help further clarify its role in this disease, he maintained.

Study Details

KEYNOTE-028 is a phase Ib multicohort study among patients with PD-L1–positive advanced solid tumors who experienced treatment failure of or were unable to receive standard therapy.

Immunohistochemical staining for PD-L1 was done in a central laboratory, according to Dr. Ott. Positivity required membranous expression by at least 1% of tumor cells and associated inflammatory cells or positive staining in the stroma. Overall, just 28.6% of the patients with SCLC screened for the trial were found to have PD-L1–positive tumors.

Patients were treated with pembrolizumab at 10 mg/kg every 2 weeks. They underwent assessment of response every 8 weeks for the first 6 months and every 12 weeks thereafter.

Among the 24 patients ultimately enrolled, all had received chemotherapy, and 87.5% had received 2 or more previous lines of therapy during the entire course of their disease. Some 20.8% had stable brain metastases

Toxicity and Survival

“The toxicity was overall very consistent with prior experience with pembrolizumab,” Dr. Ott revealed. “Most toxicity was grade 1 and 2, with the most common side effects being arthralgias, asthenia, rash, diarrhea, and fatigue.”

Adverse events of any grade occurred in 66.7% of patients, and adverse events of grade 3 or worse occurred in 8.3%. Some 12.5% experienced immune-related adverse events—thyroiditis, infusion-site reaction, cytokine-release syndrome, or colitis—with no cases of pneumonitis.

According to investigator review, the median duration of progression-free survival was 1.9 months, and the 1-year rate was 23.8%. The median duration of overall survival was 9.7 months, and the 1-year rate was 37.7%.

“There is quite an encouraging plateau of the survival curve going out to 24 months,” Dr. Ott noted. ■

Disclosure: The trial was supported by Merck. Dr. Ott has received research funding from Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, and Celldex and honoraria from Merck, Genentech, Alexion, CytomX, and Celldex.

Reference

1. Ott PA, Felip E, Hiret S, et al: Pembrolizumab in patients with extensive-stage small cell lung cancer: Updated survival results from KEYNOTE-028. 2016 World Conference on Lung Cancer. Abstract OA05.01. Presented December 5, 2016.


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Expert Point of View: Leora Horn, MD, MSc


The caveat is that this was a highly selected cohort of patients.
— Leora Horn, MD, MSc

The KEYNOTE-028 results confirm that pembrolizumab ­(Keytruda) is active in extensive-stage small cell lung cancer (SCLC) and lay to rest safety concerns stemming from the higher risk ...


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