AT THE 2016 ASCO ANNUAL MEETING

CHICAGO (FRONTLINE MEDICAL NEWS) – Overall response rates ranged from 48% to 71% when pembrolizumab was added to chemotherapy combinations in patients with advanced non–small cell lung cancer (NSCLC), and close to 30% when added to an R2 inhibitor in patients with advanced NSCLC and other tumor types, according to two early phase clinical trials presented at the annual meeting of the American Society of Clinical Oncology.

Safety and efficacy of pembrolizumab in combination with either carboplatin and paclitaxel; carboplatin, paclitaxel, and bevacizumab; or carboplatin and pemetrexed were evaluated in the KEYNOTE-021 trial. Patients were split between two doses of pembrolizumab: 2 or 10 mg/kg every 3 weeks. The overall response rate for the entire cohort of 74 patients with advanced NSCLC was 57% (95% confidence interval, 45-68), reported Dr. Shirish Gadgeel of Karmanos Cancer Institute, Detroit.

For the 25 patients who received pembrolizumab, carboplatin, and paclitaxel (cohort A) the overall response was 52% (95% CI, 31-72). For the 25 patients who also received bevacizumab in addition to pembrolizumab, carboplatin, and paclitaxel (cohort B), the overall response rate was 48% (95% CI, 28-69).

Among 24 patients who received pemetrexed with pembrolizumab and carboplatin (cohort C), the overall response was the highest at 71% (95% CI, 49-87).

Grade 3 or 4 adverse events occurred in 36%, 46%, and 42% of patients in cohort A, B, and C, respectively. The most common adverse events were anemia and neutropenia including febrile neutropenia.

“Pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in treatment-naïve advanced NSCLC,” Dr Gadgeel said.

A randomized phase III study evaluating pemetrexed/platinum with or without pembrolizumab is currently recruiting, he said.

These combinations, while perhaps better than chemotherapy alone, may be no better than just immunotherapy alone, session moderator Dr. Scott Antonia of the Moffitt Cancer Center, Tampa, Fla., commented. “And the truth is that concurrent therapy is clearly more toxic.”

In another study presented at the meeting, led by Dr. Roy Herbst of Yale Cancer Center, New Haven, Conn., pembrolizumab was combined with ramucirumab, a recently approved vascular endothelial growth factor receptor–2 inhibitor. “Hallmarks of tumor growth include angiogenesis and immunosuppression,” Dr. Herbst and his coauthors wrote in their abstract, noting that this was the first study to combine these agents to target both processes simultaneously.

“The idea is the R2 inhibitor might have an effect on the microimmune environment and drive T cells into the tumor,” Dr. Herbst said.

The study cohort included patients with advanced gastric or gastroesophageal junction adenocarcinoma, NSCLC, and urothelial carcinoma.

Overall, the response rate was close to 30% in the first 10 patients, Dr. Herbst reported. Furthermore, the preliminary data did not reveal any unexpected safety signals.

Although the data was from a small, ongoing phase I trial, Dr. Herbst noted the data is promising. Researchers are continuing to collect data on the safety profile of this drug combination, and are planning to enroll patients with additional tumor types.

The KEYNOTE-021 trial was funded by Merck Sharp and Dohme. Dr. Gadgeel reported having a consulting or advisory role and receiving research funding from multiple companies. The trial headed by Dr. Herbst was funded by Eli Lilly. Dr. Herbst reported having a consulting or advisory role and receiving honoraria and research funding from multiple companies including Eli Lilly.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

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