Atezolizumab plus chemotherapy

A phase III open-label study (IMpower130 [NCT02367781]) included 724 patients with previously untreated, stage IV, nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive atezolizumab (1,200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin, AUC 6 mg/mL per minute every 3 weeks with nab-paclitaxel 100 mg/m2 intravenously every week), or chemotherapy alone given once every 3 weeks for four or six cycles. All patients received maintenance therapy as follows: (1) patients in the atezolizumab-plus-chemotherapy group received atezolizumab 1,200 mg intravenously every 3 weeks until investigator-assessed loss of clinical benefit or toxicity, and (2) patients in the chemotherapy-alone group received best supportive care or pemetrexed switch maintenance therapy until disease progression or toxicity. Coprimary end points were investigator-assessed PFS and OS in the ITT population with EGFR wild-type and ALK wild-type tumors.[99][Level of evidence A1]

A phase III open-label study (IMpower130 [NCT02367781]) included 724 patients with previously untreated, stage IV, nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive atezolizumab (1,200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin, AUC 6 mg/mL per minute every 3 weeks with nab-paclitaxel 100 mg/m2 intravenously every week), or chemotherapy alone given once every 3 weeks for four or six cycles. All patients received maintenance therapy as follows: (1) patients in the atezolizumab-plus-chemotherapy group received atezolizumab 1,200 mg intravenously every 3 weeks until investigator-assessed loss of clinical benefit or toxicity, and (2) patients in the chemotherapy-alone group received best supportive care or pemetrexed switch maintenance therapy until disease progression or toxicity. Coprimary end points were investigator-assessed PFS and OS in the ITT population with EGFR wild-type and ALK wild-type tumors.[99][Level of evidence A1]

In the ITT wild-type population, the median OS was 18.6 months (95% CI, 16.0–21.2) in the atezolizumab-plus-chemotherapy group and 13.9 months (95% CI, 12.0–18.7) in the chemotherapy group (stratified HR, 0.79; 95% CI, 0.64–0.98; P = .033).

A phase III open-label study (IMpower130 [NCT02367781]) included 724 patients with previously untreated, stage IV, nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive atezolizumab (1,200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin, AUC 6 mg/mL per minute every 3 weeks with nab-paclitaxel 100 mg/m2 intravenously every week), or chemotherapy alone given once every 3 weeks for four or six cycles. All patients received maintenance therapy as follows: (1) patients in the atezolizumab-plus-chemotherapy group received atezolizumab 1,200 mg intravenously every 3 weeks until investigator-assessed loss of clinical benefit or toxicity, and (2) patients in the chemotherapy-alone group received best supportive care or pemetrexed switch maintenance therapy until disease progression or toxicity. Coprimary end points were investigator-assessed PFS and OS in the ITT population with EGFR wild-type and ALK wild-type tumors.[99][Level of evidence A1]

The median PFS was 7 months (95% CI, 6.2–7.3) in the atezolizumab-plus-chemotherapy group and 5.5 months (95% CI, 4.4–5.9) in the chemotherapy group (stratified HR, 0.64; 95% CI, 0.54–0.77; P < .0001).

A phase III open-label study (IMpower130 [NCT02367781]) included 724 patients with previously untreated, stage IV, nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive atezolizumab (1,200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin, AUC 6 mg/mL per minute every 3 weeks with nab-paclitaxel 100 mg/m2 intravenously every week), or chemotherapy alone given once every 3 weeks for four or six cycles. All patients received maintenance therapy as follows: (1) patients in the atezolizumab-plus-chemotherapy group received atezolizumab 1,200 mg intravenously every 3 weeks until investigator-assessed loss of clinical benefit or toxicity, and (2) patients in the chemotherapy-alone group received best supportive care or pemetrexed switch maintenance therapy until disease progression or toxicity. Coprimary end points were investigator-assessed PFS and OS in the ITT population with EGFR wild-type and ALK wild-type tumors.[99][Level of evidence A1]

Subgroup analyses showed OS and PFS benefit with atezolizumab across several clinical subgroups, with the exception of patients with liver metastases where the additional of atezolizumab did not improve OS versus chemotherapy alone, and for patients with EGFR and ALK genomic alterations.

A phase III open-label study (IMpower130 [NCT02367781]) included 724 patients with previously untreated, stage IV, nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive atezolizumab (1,200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin, AUC 6 mg/mL per minute every 3 weeks with nab-paclitaxel 100 mg/m2 intravenously every week), or chemotherapy alone given once every 3 weeks for four or six cycles. All patients received maintenance therapy as follows: (1) patients in the atezolizumab-plus-chemotherapy group received atezolizumab 1,200 mg intravenously every 3 weeks until investigator-assessed loss of clinical benefit or toxicity, and (2) patients in the chemotherapy-alone group received best supportive care or pemetrexed switch maintenance therapy until disease progression or toxicity. Coprimary end points were investigator-assessed PFS and OS in the ITT population with EGFR wild-type and ALK wild-type tumors.[99][Level of evidence A1]

OS and PFS benefit with atezolizumab was also observed in the ITT wild-type population independent of PD-L1 expression.

A phase III open-label study (IMpower130 [NCT02367781]) included 724 patients with previously untreated, stage IV, nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive atezolizumab (1,200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin, AUC 6 mg/mL per minute every 3 weeks with nab-paclitaxel 100 mg/m2 intravenously every week), or chemotherapy alone given once every 3 weeks for four or six cycles. All patients received maintenance therapy as follows: (1) patients in the atezolizumab-plus-chemotherapy group received atezolizumab 1,200 mg intravenously every 3 weeks until investigator-assessed loss of clinical benefit or toxicity, and (2) patients in the chemotherapy-alone group received best supportive care or pemetrexed switch maintenance therapy until disease progression or toxicity. Coprimary end points were investigator-assessed PFS and OS in the ITT population with EGFR wild-type and ALK wild-type tumors.[99][Level of evidence A1]

Grade 3 or 4 adverse events occurred in 81% of patients who received atezolizumab plus chemotherapy versus 71% of patients who received chemotherapy alone. Immune-related adverse events occurred in 45% of patients treated with atezolizumab plus chemotherapy and most were grade 1 or 2 in severity. The most common immune-related adverse events were rash (24%), hypothyroidism (15%), and hepatitis (10%).