Immunotherapy alone falls short in first-line treatment of NSCLC

First-line immunotherapy with durvalumab alone or durvalumab plus tremelimumab failed to extend overall survival in unselected patients with metastatic non-small cell lung cancer (NSCLC), according to results of the MYSTIC trial presented at the European Society for Medical Oncology (ESMO) Immuno-Oncology 2018 Congress, December 13-16, Geneva, Switzerland.

Durvalumab is a human IgG1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and CD80 molecules, and tremelimumab is a human IgG2 monoclonal antibody that blocks the activity of CTLA-4. In prior studies, researchers have demonstrated both drugs to be efficacious in treating NSCLC. Although immune checkpoint inhibitors and chemotherapy have been successfully demonstrated as frontline therapy for metastatic NSCLC, the use of two immunotherapy drugs without chemotherapy as first-line treatment requires further study.

Thus, researchers, led by Naiyer A. Rizvi, MD, Division of Hematology and Oncology, Columbia University Medical Center, New York, NY, conducted the open-label, phase 3 MYSTIC trial to compare first-line treatment of NSCLC with durvalumab vs platinum-based chemotherapy and durvalumab plus tremelimumab vs platinum-based chemotherapy.

Dr. Rizvi and colleagues randomly assigned 1,118 patients with metastatic NSCLC to one of three treatment groups: durvalumab alone, durvalumab plus tremelimumab, or chemotherapy. The primary outcomes were overall survival for durvalumab compared with chemotherapy, and overall survival and progression-free survival for durvalumab plus tremelimumab compared with chemotherapy in patients expressing ≥ 25% PD-L1 tumor-cell expression (n=488). None of the patients exhibited EGFR sensitizing mutation or ALK rearrangement, and all patients were treatment naïve.

In patients with PD-L1 tumor-cell expression ≥ 25%, median overall survival was 16.3 vs 12.9 months in patients who received durvalumab vs chemotherapy (HR: 0.76; 97.54% CI: 0.564-1.019; P=0.036) and 11.9 vs 12.9 months for those who received durvalumab plus tremelimumab vs chemotherapy (HR: 0.85; 98.77% CI: 0.611-1.173; P=0.202). Furthermore, median progression-free survival was 3.9 vs 5.4 months for treatment with durvalumab plus tremelimumab vs chemotherapy (HR: 1.05; 99.5% CI: 0.722-1.534; P=0.705).

The investigators found that safety data were comparable to previous studies, with the frequency of grade 3/4 treatment-related adverse events being 14.6% for durvalumab, 22.1% for durvalumab plus tremelimumab, and 33.8% with chemotherapy.

Although results for the primary outcomes of overall survival and progression-free survival did not reach statistical significance, first-line therapy with durvalumab did show a notable enhancement in overall survival in patients with ≥ 25% PD-L1 tumor-cell expression who received durvalumab monotherapy vs chemotherapy.