Atezolizumab plus bevacizumab plus chemotherapy

In a phase III open-label study (IMpower150 [NCT02366143]),1,202 patients with stage IV or recurrent metastatic nonsquamous NSCLC were randomly assigned in a 1:1:1 ratio to receive either atezolizumab plus carboplatin plus paclitaxel (ACP group), atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP group), or bevacizumab plus carboplatin plus paclitaxel (BCP group). Treatment consisted of four or six 21-day cycles. Atezolizumab was given intravenously at a dose of 1,200 mg, bevacizumab at a dose of 15 mg per kilogram of body weight, carboplatin at an area under the concentration-time curve of 6 mg/mL per minute and paclitaxel at a dose of 200 mg/m2 (175 mg/m2 for Asian patients). Patients continued to receive atezolizumab, bevacizumab, or both until disease progression or development of intolerable toxicity. Coprimary end points were PFS, both in the ITT population with EGFR wild-type and ALK wild-type tumors and among patients with wild-type tumors who had high expression of an effector T-cell (Teff) gene signature in the tumor, and OS in the wild-type population.[100][Level of evidence A1]

In a phase III open-label study (IMpower150 [NCT02366143]),1,202 patients with stage IV or recurrent metastatic nonsquamous NSCLC were randomly assigned in a 1:1:1 ratio to receive either atezolizumab plus carboplatin plus paclitaxel (ACP group), atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP group), or bevacizumab plus carboplatin plus paclitaxel (BCP group). Treatment consisted of four or six 21-day cycles. Atezolizumab was given intravenously at a dose of 1,200 mg, bevacizumab at a dose of 15 mg per kilogram of body weight, carboplatin at an area under the concentration-time curve of 6 mg/mL per minute and paclitaxel at a dose of 200 mg/m2 (175 mg/m2 for Asian patients). Patients continued to receive atezolizumab, bevacizumab, or both until disease progression or development of intolerable toxicity. Coprimary end points were PFS, both in the ITT population with EGFR wild-type and ALK wild-type tumors and among patients with wild-type tumors who had high expression of an effector T-cell (Teff) gene signature in the tumor, and OS in the wild-type population.[100][Level of evidence A1]

Median PFS was longer in the ABCP group (8.3 months) than the BCP group (6.8 months) (HR, 0.62; 95% CI, 0.52–0.74; P < .001). In the Teff-high wild-type population, PFS was 11.3 months versus 6.8 months (HR, 0.51; 95% CI, 0.38–0.68; P .001). PFS was also longer in the ABCP group versus the BCP group in the ITT population with EGFR and ALK genomic alterations, among patients with low or negative PD-L1 expression, low Teff gene-signature expression, and in patients with liver metastases.

In a phase III open-label study (IMpower150 [NCT02366143]),1,202 patients with stage IV or recurrent metastatic nonsquamous NSCLC were randomly assigned in a 1:1:1 ratio to receive either atezolizumab plus carboplatin plus paclitaxel (ACP group), atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP group), or bevacizumab plus carboplatin plus paclitaxel (BCP group). Treatment consisted of four or six 21-day cycles. Atezolizumab was given intravenously at a dose of 1,200 mg, bevacizumab at a dose of 15 mg per kilogram of body weight, carboplatin at an area under the concentration-time curve of 6 mg/mL per minute and paclitaxel at a dose of 200 mg/m2 (175 mg/m2 for Asian patients). Patients continued to receive atezolizumab, bevacizumab, or both until disease progression or development of intolerable toxicity. Coprimary end points were PFS, both in the ITT population with EGFR wild-type and ALK wild-type tumors and among patients with wild-type tumors who had high expression of an effector T-cell (Teff) gene signature in the tumor, and OS in the wild-type population.[100][Level of evidence A1]

Median OS among patients with wild-type tumors was longer in the ABCP group (19.2 months), compared with the BCP group (14.7 months) (HR, 0.78; 95% CI, 0.64–0.96; P = .02).

In a phase III open-label study (IMpower150 [NCT02366143]),1,202 patients with stage IV or recurrent metastatic nonsquamous NSCLC were randomly assigned in a 1:1:1 ratio to receive either atezolizumab plus carboplatin plus paclitaxel (ACP group), atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP group), or bevacizumab plus carboplatin plus paclitaxel (BCP group). Treatment consisted of four or six 21-day cycles. Atezolizumab was given intravenously at a dose of 1,200 mg, bevacizumab at a dose of 15 mg per kilogram of body weight, carboplatin at an area under the concentration-time curve of 6 mg/mL per minute and paclitaxel at a dose of 200 mg/m2 (175 mg/m2 for Asian patients). Patients continued to receive atezolizumab, bevacizumab, or both until disease progression or development of intolerable toxicity. Coprimary end points were PFS, both in the ITT population with EGFR wild-type and ALK wild-type tumors and among patients with wild-type tumors who had high expression of an effector T-cell (Teff) gene signature in the tumor, and OS in the wild-type population.[100][Level of evidence A1]

Grade 3 or 4 treatment-related adverse events occurred in 56% of patients in the ABCP group versus 48% of patients in the BCP group. Most immune-related adverse events in the ABCP group were grade 1 or 2, and rash, hypothyroidism, hyperthyroidism, hepatitis, pneumonitis, and colitis were most common. Treatment-related deaths occurred in 11 patients (2.8%) in the ABCP group and 9 patients (2.3%) in the BCP group. Five deaths in the ABCP group were caused by pulmonary hemorrhage or hemoptysis, and four of five occurred in patients with high-risk features, including tumors infiltrating great vessels or tumor cavitation.