FDA Approves Two Checkpoint Inhibitor Regimens for First-Line Metastatic NSCLC Treatment

The FDA approved two regimens for first-line treatment of adults with metastatic NSCLC without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations: the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) for patients whose tumors express at least 1% PD-L1 and atezolizumab (Tecentriq, Genentech) for patients whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC ≥50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥10% of the tumor area [IC ≥10%]).

The new indication for nivolumab plus ipilimumab was granted based on results from CHECKMATE-227, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy. In part 1a of the trial, 793 patients with PD-L1 tumor expression of at least 1% were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n=396) or platinum-doublet chemotherapy (n=397).

The trial demonstrated a statistically significant improvement in overall survival (OS) in patients with PD-L1 tumor expression receiving nivolumab plus ipilimumab compared with those treated with platinum-doublet chemotherapy. Median OS was 17.1 months (95% CI, 15-20.1 months) versus 14.9 (95% CI, 12.7-16.7) (hazard ratio [HR], 0.79; 95% CI, 0.67-0.94; P=0.0066).

Median progression-free survival (PFS) per blinded independent central review was 5.1 months (95% CI, 4.1-6.3 months) in the nivolumab plus ipilimumab arm and 5.6 months (95% CI, 4.6-5.8 months) in the platinum-doublet chemotherapy arm (HR, 0.82; 95% CI, 0.69-0.97). Confirmed overall response rate (ORR) per independent review was 36% (95% CI, 31%-41%) and 30% (95% CI, 26%-35%), respectively. Median response duration was 23.2 months in the nivolumab plus ipilimumab arm and 6.2 months in the platinum-doublet chemotherapy arm.

The most common adverse reactions in patients receiving nivolumab plus ipilimumab therapy were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea and hepatitis.

Atezolizumab
The new indication for atezolizumab was granted based on results from IMpower110, a multicenter, international, randomized, open-label trial in patients with stage IV NSCLC whose tumors expressed PD-L1 (TC ≥1% or IC ≥1%), who had received no prior chemotherapy for metastatic disease. Patients were randomized to receive 1,200 mg of atezolizumab every three weeks until disease progression or unacceptable toxicity, or platinum-based chemotherapy. OS was the primary efficacy outcome measure.

The trial demonstrated a statistically significant improvement in OS for patients with high PD-L1 tumor expression receiving atezolizumab compared with those treated with platinum-based chemotherapy. Median OS was 20.2 months (95% CI, 16.5-NE) for patients in the atezolizumab arm compared with 13.1 months (95% CI, 7.4-16.5 months) in the chemotherapy arm (HR, 0.59; 95% CI, 0.40-0.89; P=0.0106). There was no statistically significant difference in OS for the other two PD-L1 subgroups (TC ≥5% or IC ≥5%, and TC ≥1% or IC ≥1%) at the interim or final analyses.

Median PFS was 8.1 months (95% CI, 6.8-11.0 months) in the atezolizumab arm and five months (95% CI, 4.2-5.7 months) in the platinum-based chemotherapy arm (HR, 0.63; 95% CI, 0.45-0.88). Confirmed ORR was 38% (95% CI, 29%-48%) and 29% (95% CI, 20%-39%), respectively.

The most common adverse reaction with atezolizumab as a single agent in IMpower110 was fatigue/asthenia.

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Both applications received priority review designation from the FDA.

—Clinical Oncology News Staff

Based on press releases from the FDA, Bristol-Myers Squibb and Genentech.