The Hoosier Cancer Research Network study, LUN14-179, “A Phase II Trial of Concurrent Chemoradiation With Consolidation Pembrolizumab (MK-3475) for the Treatment of Inoperable or Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC): HCRN LUN14-179,” affirms the effectiveness of consolidation immunotherapy after chemoradiation in adults with unresectable stage IIIA or IIIB non-small cell lung cancer. The study demonstrates that the addition of pembrolizumab in Stage III NSCLC may be associated with prolonged time to metastatic disease or death (TMDD), progression-free survival (PFS) and overall survival (OS), after treatment with chemoradiation. The findings were recently published in the Clinical Lung Cancer journal and American Cancer Society’s Cancer journal. The median TMDD was 30.7 months, the median PFS was 18.7 months, and the median OS was 35.8 months.

The study, NCT02343952, which lasted 36 months across 16 HCRN sites, sought to determine if consolidation therapy with the use of the PD-1 inhibitor, pembrolizumab followed by chemoradiation treatment would improve the time to death or distant metastatic disease in patients with inoperable or unresectable stage IIIA or IIIB non-small cell lung cancer. The study confirmed the findings of the PACIFIC trial, a benchmark study that was the first to test this approach in a clinical setting and now represents the standard of care for adults with unresectable or inoperable stage IIIA or IIIB NSCLC.

“Our study confirms the established role of consolidation immunotherapy after chemoradiation in unresectable patients with stage III NSCLC,” said co-investigator of the study, Gregory A. Durm, MD, medical oncologist and researcher at Indiana University Melvin and Bren Simon Comprehensive Cancer Center in Indianapolis, Ind. “Our study, while not randomized, shows similar efficacy endpoints to durvalumab in the PACIFIC trial and further cements immunotherapy consolidation as the standard of care in this setting.”

NSCLC is the most common form of lung cancer in the United States and arises when cells in the lung grow out of control. Three types of NSCLC tumors exist, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. At the start of the trial, outcomes for the disease were poor. Five-year survival for patients with NSCLC IIIA and IIIB were 14% and 5%, respectively.

Pembrolizumab works by blocking the PD-1 pathway that cancer cells use to hide from the body’s immune system. Blocking the pathway helps the body’s immune system recognize and attack cancer cells. Pembrolizumab is approved by the U.S. Food and Drug Administration (FDA) to treat several types of cancer, including advanced NSCLC.

This multi-site study enrolled 93 participants, 92 of which were included in the efficacy analysis (one participant was later deemed ineligible).

Subjects with unresectable stage III NSCLC received either concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel plus radiation. Subjects with no progression of disease received pembrolizumab every three weeks for up to 12 months.

Exploratory objectives included assessing PD-L1 expression levels in tumor samples of subjects and correlating it with time to distant metastatic disease, tumor histology, PFS, OS, and treatment toxicity.

“The correlative analyses from our trial highlight some important points for further exploration,” Dr. Durm said. “First, our trial, though admittedly smaller, does not demonstrate an improvement in efficacy for those patients who started consolidation earlier. That is in contrast to the PACIFIC trial. Our trial also doesn’t show any difference in outcomes related to PD-L1 status which is, again, in contrast to the PACIFIC trial.”

Dr. Durm also said noted that similar to the PACIFIC trial, the majority of patients were not able to receive the full one-year of consolidation immunotherapy, and many of these patients did not have recurrence of their cancer.

“This calls in to question the appropriate duration of consolidation immunotherapy in this setting,” he noted. “It will be important to look further at the questions of timing of initiation, biomarkers, and optimal duration of therapy with future trials.”

See Clinical Lung Cancer article.

See ACS Cancer article.

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.