Adding Keytruda (pembrolizumab) to standard first-line therapy with Paraplatin (carboplatin) and Alimta (pemetrexed) is a promising approach for patients with inoperable or metastatic nonsquamous non-small cell lung cancer (NSCLC), according to recent data from a Phase 1/2 study.
The findings, presented at the European Society for Medical Oncology (ESMO) 2016 Congress Oct. 7-11 in Denmark, show the Keytruda-chemotherapy combination significantly prolongs patients’ progression-free survival and overall survival compared to Paraplatin/Alimta chemotherapy alone.
Currently, NSCLC patients without targetable mutations such as epidermal growth factor receptor (EGFR) mutation or other significant biomarkers are treated with platinum-based chemotherapy as a first line therapy. According to Dr. Corey J. Langer, MD, director of the thoracic oncology program at Abramson Cancer Center of the University of Pennsylvania, Keytruda had already shown promise as a single agent in pretreated patients, suggesting that it could improve the effectiveness of first-line chemotherapy.
To address this, a cohort of the randomized, open-label Phase 1/2 KEYNOTE-021 (NCT02039674) trial compared the addition of Keytruda to standard of care chemotherapy in NSCLC patients. The analysis included data from 123 patients who had never received chemotherapy and had an ECOG (Eastern Cooperative Oncology Group) status of one or lower, meaning they could perform most physical tasks. The participants did not have any EGFR mutations or ALK (anaplastic lymphoma kinase) abnomalty.
After categorizing patients according to their tumor proportion score (1% or greater vs. less than 1%), participants were randomized to receive four cycles of Paraplatin plus Alimta every three weeks either alone or in combination with 24 months of Keytruda every three weeks.
The study’s primary endpoint was overall response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Outcomes according to each patient’s PD-L1 status were also assessed.
After a median follow-up of 10.6 months, 47% of patients were still on the Keytruda arm while only 31% remained in the chemotherapy arm. Half the patients in the chemotherapy arm eventually crossed over to the Keytruda arm or they were given another checkpoint inhibitor.
The study met its primary endpoint with the overall response rate in the Keytruda arm almost doubling that of the chemotherapy arm (55% vs. 29%). Median progression-free survival was also significantly longer in the Keytruda arm (13 months vs. 8.9 months).
At six months, more patients who were given Keytruda did not show disease progression (77% vs. 63%), but 92% of patients in both groups had survived.
The most common adverse reactions were fatigue, nausea, and anemia. Although the Keytruda arm showed a higher incidence of grade 3 or worse adverse effects, it did not translate into higher rates of discontinuation.
Because the trial showed that adding Keytruda to the standard first line chemotherapy nearly doubles the responses to treatment and reduced the risk of progression by half, the researchers believe that the combination may improve outcomes for patients with advanced NSCLC.
A randomized Phase 3 trial (NCT02578680) assessing the effectiveness of this combination versus standard chemotherapy is ongoing.