FDA Approves Atezolizumab Combination for Frontline Treatment of NSCLC

The U.S. Food and Drug Administration approved atezolizumab in combination with bevacizumab, carboplatin, and paclitaxel (ABCP) for the first-line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC). This regimen is not indicated for patients with EGFR/ALK alterations. 

The approval was based on results of the multicenter, open-label, randomized, controlled, phase III IMpower150 trial that included 1,202 patients with stage IV non-squamous NSCLC. Patients were randomized to receive: 

• Atezolizumab, carboplatin, and paclitaxel (ACP; n=402) 

• ABCP (n=400) 
• Bevacizumab, carboplatin, and paclitaxel (BCP; control group; n=400) https://twitter.com/dhjutsw1/status/1071029550597976064

The median overall survival (OS) in the ABCP group was 19.2 months (95% CI, 17.0-23.8) compared with 14.7 months (95% CI, 13.3-16.9) in the BCP arm (hazard ratio [HR] = 0.78; 95% CI, 0.64-0.96; P=0.0164). The 24-month OS rate was 43% with ABCP compared with 34% for BCP.  

FDA approved atezolizumab with chemotherapy and bevacizumab for first-line treatment of metastatic non-squamous #NSCLC with no EGFR or ALK genomic tumor aberrations #lcsm https://t.co/aFlOY7WkgR

— FDA Oncology (@FDAOncology) December 6, 2018

ABCP improved the median progression-free survival by 1.5 months compared with BCP (8.5 vs. 7.0 months; HR=0.71; 95% CI, 0.59-0.85; P<0.0002). ABCP had an overall response rate of 55% (95% CI, 49-60) compared with 42% in the BCP cohort (95% CI, 37-48). The median duration of response was 10.8 months in the ABCP cohort (95% CI, 8.4-13.9) compared with 6.5 months in the BCP cohort (95% CI, 5.6-7.6). 

In today's @NEJM — IMpower 133 demonstrating the addition of atezolizumab to carboplatin + etoposide improved OS over chemo alone (OS HR 0.70, p=0.007). Garnered FDA priority review and category 1, preferred recommendation in NCCN. Current SOC, IMO.https://t.co/rWjGQSKOgs

— Stephen V Liu, MD (@StephenVLiu) December 6, 2018

The most common adverse events (AEs) associated with the ABCP regimen were fatigue and asthenia (50%), alopecia (48%), nausea (39%), diarrhea (32%), constipation (30%), decreased appetite (29%), arthralgia (26%), hypertension (25%), and peripheral neuropathy (24%). Treatment-related grade 3 or 4 AEs occurred in 43% of patients in the ACP group, 57% of the ABCP group, and 49% of BCP group. Serious AEs occurred in 39%, 44%, and 34% of patients, respectively.  

FDA approves a new treatment for ALK-positive metastatic NSCLC. 

FDA expands the approval of pembrolizumab for frontline treatment of NSCLC. 

Source: Roche press release