After granting Priority Review, the FDA has approved atezolizumab (Tecentriq®, Genentech, Inc.), a monoclonal antibody, to be used in combination with carboplatin/paclitaxel/bevacizumab (CPB) for patients with previously untreated metastatic nonsquamous, non-small cell lung cancer (NSCLC) without EGFR or ALK tumor mutations.
The approval was based on the open-label, three-arm IMpower150 trial (NCT02366143), for which patients were randomized 1:1:1 to a regimen of atezolizumab plus CPB, a regimen of atezolizumab plus carboplatin/paclitaxel (CP), or a control arm regimen of CPB alone. The trial's objective was comparison of the two atezolizumab-containing arms with the control arm. Of the 1,202 patients with previously untreated metastatic nonsquamous NSCLC enrolled in the trial, 87% had no EGFR or ALK mutations.
After receiving four or six cycles every three weeks of the full treatment to which they were assigned (CP plus atezolizumab/bevacizumab, atezolizumab, or bevacizumab), CP was discontinued, and patients continued to receive the assigned maintenance therapy involving atezolizumab and/or bevacizumab. All treatments continued until disease progression or unacceptable toxicity.
In participants without EGFR or ALK mutations, atezolizumab-CPB prolonged estimated median overall survival compared with CPB alone (19.2 vs 14.7 months) and estimated median progression-free survival (8.5 vs 7.0 months), as well as producing superior overall response rates (55% vs 42%). Atezolizumab plus CP showed no significant differences in interim overall survival or final progression-free survival compared with CPB.
The recommended dose of atezolizumab is 1,200 mg given intravenously over 60 minutes every three weeks.
In the atezolizumab-CPB arm, common adverse reactions reported in at least 20% of patients included fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Fifteen percent of patients discontinued atezolizumab for adverse reactions, with pneumonitis as the most common cause (1.8%).
Among 364 patients with NSCLC receiving atezolizumab-CPB, 36% had treatment-emergent antibodies against atezolizumab, with 83% of these patients having anti-drug antibodies prior to the second atezolizumab dose. Patients with treatment-emergent anti-drug antibodies had reduced systemic atezolizumab exposure. In an exploratory analysis, the hazard ratios for overall survival were similar for patients with and without anti-drug antibodies, which did not increase incidence or severity of adverse reactions. Owing to their frequent occurrence, Genentech has agreed to evaluate the effects of anti-drug antibodies on efficacy, safety, and pharmacokinetics across the atezolizumab development program.
For More Information
Clinicaltrials.gov (2018). A study of atezolizumab in combination with carboplatin plus (+) paclitaxel with or without bevacizumab compared with carboplatin+paclitaxel+bevacizumab in participants with stage IV non-squamous non-small cell lung cancer (NSCLC) (IMpower150). NLM identifier: NCT02366143.
Socinski MA, Jotte RM, Cappuzzo F, et al (2018). Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med, 378(24):2288-2301. DOI:10.1056/NEJMoa1716948