Yesterday, Novocure announced the U.S. Food and Drug Administration (FDA) approval of Optune Lua® for concurrent use with PD-1/PD-L1 inhibitors or docetaxel for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) who have experienced disease progression on or after a platinum-based regimen. This wearable treatment device delivers tumor treating fields, which exert physical forces on the electrically charged components of dividing cancer cells, resulting in cell death.
Efficacy and Safety
Data supporting this approval are from the phase III LUNAR trial, a randomized, open-label, multicenter study. It compared the use of tumor treating fields therapy concurrently with PD-1/PD-L1 inhibitors or docetaxel (experimental arm) with the use of PD-1/PD-L1 inhibitors or docetaxel alone (control arm) for patients with metastatic NSCLC who experienced disease progression during or after platinum-based therapy.
The primary endpoint of the study was achieved, demonstrating a statistically significant and clinically meaningful 3.3-month (P = .04) extension in median overall survival for patients who received tumor treating fields concurrently with a PD-1/PD-L1 inhibitor or docetaxel (n = 145). The group given tumor treating fields therapy concurrently with a PD-1/PD-L1 inhibitor or docetaxel had a median overall survival of 13.2 months (95% confidence interval [CI] = 10.3–15.5 months) vs 9.9 months (95% CI = 8.2–12.2 months) in the group given a PD-1/PD-L1 inhibitor or docetaxel (n = 146).
The LUNAR study included two prespecified powered secondary endpoints. The first secondary endpoint, which met statistical significance, assessed median overall survival in patients treated with tumor treating fields concurrently with a PD-1/PD-L1 inhibitor vs a PD-1/PD-L1 inhibitor alone. The second secondary endpoint, which showed a positive trend but did not meet statistical significance, assessed the use of tumor treating fields therapy concurrently with docetaxel vs docetaxel alone.
Patients randomly assigned to receive the tumor treating fields therapy and a PD-1/PD-L1 inhibitor (n = 70) demonstrated a median overall survival of 19.0 months (95% CI = 10.6–28.2 months) vs 10.8 months (95% CI = 8.3–17.6 months) in patients treated a with PD-1/PD-L1 inhibitor alone (n = 71), which was a statistically significant extension in median overall survival of more than 8 months (P = .02). Patients randomly assigned to receive tumor treating fields therapy and docetaxel (n = 75) had a median overall survival of 11.1 months (95% CI = 8.2–13.9 months) vs 8.9 months (95% CI = 6.5–11.3 months) in patients treated with docetaxel alone (n = 75). This 2.2-month improvement in median overall survival did not provide a statistically significant demonstrated benefit but did show a positive trend.
Device-related adverse events (skin-related disorders under the transducer arrays) occurred in 63.1% of patients (n = 89). The majority of these events were grade 1 or 2, with 4% (n = 6) experiencing grade 3 skin toxicity that required a break from treatment. No grade 4 or 5 toxicities related to the tumor treating fields therapy nor device-related adverse events that caused death were reported.
Baseline patient characteristics were well balanced between the cohorts: median age was 65 years (range, 22–86 years); 66% were male; 96% of patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. PD-L1 expression data were collected from 83% of patients (69 of 83 patients) enrolled at U.S. sites and were well balanced across the four cohorts.
