FDA Approves Atezolizumab Combination in First-Line Treatment of Metastatic Nonsqumous NSCLC
Posted: Friday, December 7, 2018
On December 6, 2018, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic, nonsquamous non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.
Approval was based on the IMpower150 trial (ClinicalTrials.gov identifier NCT02366143), an open-label, randomized, 3-arm trial enrolling 1,202 patients receiving first-line treatment for metastatic, nonsquamous NSCLC. Eighty-seven percent (n = 1,045) were identified as not having EGFR or ALK tumor mutations. The trial was designed to conduct comparisons between each of the atezolizumab-containing arms with the control arm. Patients were randomly assigned to receive atezolizumab, carboplatin, paclitaxel, and bevacizumab (four-drug regimen); atezolizumab, carboplatin, and paclitaxel (three-drug regimen); or carboplatin, paclitaxel, and bevacizumab (control arm). After completion of four or six cycles of carboplatin and paclitaxel, patients continued to receive bevacizumab in the four-drug arm and the control arm and continued to receive atezolizumab in the two experimental arms until disease progression or unacceptable toxicity.
Among patients with nonsquamous NSCLC without an EGFR or ALK mutation, the estimated median overall survival was 19.2 months with the 4-drug regimen and 14.7 months with the control. The estimated median progression-free survival was 8.5 months with the 4-drug regimen and 7.0 months with the control. The overall response rates were 55% in the 4-drug arm and 42% in the control arm. No significant differences in interim overall survival or final progression-free survival were observed between the three-drug and control arms.
The most common adverse reactions (reported in ≥ 20% of patients) with atezolizumab administered with carboplatin, paclitaxel, and bevacizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Atezolizumab was discontinued for adverse reactions in 15% of patients; the most common adverse reaction resulting in treatment discontinuation was pneumonitis (1.8%).
