On 6 December 2018, the FDA approved atezolizumab (Tecentriq®, Roche/Genentech) plus bevacizumab and chemotherapy with paclitaxel and carboplatin for the frontline treatment of metastatic non-squamous non-small cell lung cancer (NSq NSCLC) patients not harbouring any EGFR or ALK genomic tumour aberrations.

IMpower150

The open-label, three-arm, IMpower150 trial (NCT02366143) randomised 1202 NSq NSCLC patients 1:1:1 to receive 4 or 6 cycles of first-line treatment with atezolizumab plus chemotherapy and bevacizumab (Arm 1), or atezolizumab plus chemotherapy (Arm 2), or chemotherapy plus bevacizumab (Arm 3). After completion of the chemotherapy, patients in Arm 1  received maintenance with atezolizumab plus bevacizumab until disease progression or unacceptable toxicity. Patients in Arms 2 and 3 received maintenance with atezolizumab and bevacizumab, respectively. The primary efficacy measures included the progression-free survival (PFS) and the overall survival (OS).

Of the 1202 NSq NSCLC patients, 87% (1045/1202) did not have EGFR or ALK tumour mutations (EGFR-/ALK-). in this group, the median OS estimate measured 19.2 months in Arm 1, and 14.7 months in Arm 3 (HR=0.78; 95% CI, 0.64-0.96; P=0.016). The median PFS by Kaplan-Meier estimate was 8.5 months (Arm 1) vs 7.0 months in Arm 3 (HR=0.71; 95% CI, 0.59-0.85; P=0.0002) with overall response rates of 55% and 42% in Arm 1 and Arm 3, respectively. No statistically significant difference in the OS or PFS were noted between Arm 2 and Arm 3.

Safety

Common adverse reactions in ≥ 20% of patients treated with atezolizumab plus bevacizumab and carboplatin with paclitaxel included fatigue/asthenia, alopecia, nausea, diarrhoea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Fifteen per cent of patients discontinued atezolizumab for adverse reactions; pneumonitis (1.8%) being the most cause of discontinuation.

Anti-Drug Antibodies

The development of anti-drug antibodies (ADA) to atezolizumab has been reported across clinical studies supporting the approved indications with an incidence ranging from 30% to 42%. Among the 364 patients with NSq NSCLC in Arm 1 of the IMpower150 study, 36% (132/364) developed treatment-emergent ADAs against atezolizumab, often (in 82% of the 132 patients) before receiving the second dose of atezolizumab. Although the presence of ADAs resulted in a lower systemic atezolizumab exposure compared to ADA-negative patients, this did not seem to affect the median OS. An exploratory analysis revealed that the HR for OS in ADA-positive vs ADA negative patients measured 0.69 (95% CI, 0.44-1.07) vs 0.64 (95% CI, 0.46-0.90), respectively. Furthermore, the presence of ADAs could not be related to the incidence or severity of adverse reactions.

Full prescribing information Tecentriq®.