Immune checkpoint modulation and combination chemotherapy

Atezolizumab. IMpower133 (NCT02763579), a double-blind, placebo-controlled, randomized, phase III trial, compared four cycles of carboplatin and etoposide with either atezolizumab (n = 201) or placebo (n = 202), followed by maintenance with either atezolizumab or placebo (as per the original randomization) until unacceptable toxic effects, disease progression, or no additional benefit.[2]

Atezolizumab. IMpower133 (NCT02763579), a double-blind, placebo-controlled, randomized, phase III trial, compared four cycles of carboplatin and etoposide with either atezolizumab (n = 201) or placebo (n = 202), followed by maintenance with either atezolizumab or placebo (as per the original randomization) until unacceptable toxic effects, disease progression, or no additional benefit.[2]

At the planned interim analysis for OS, with a median follow-up of 22.9 months, the median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio [HR] for death, 0.76; 95% confidence interval [CI], 0.60−0.95; descriptive P = .0154).[2][Level of evidence A1]

Atezolizumab. IMpower133 (NCT02763579), a double-blind, placebo-controlled, randomized, phase III trial, compared four cycles of carboplatin and etoposide with either atezolizumab (n = 201) or placebo (n = 202), followed by maintenance with either atezolizumab or placebo (as per the original randomization) until unacceptable toxic effects, disease progression, or no additional benefit.[2]

The median progression-free survival (PFS) was 5.2 months for the atezolizumab group and 4.3 months for the placebo group (HR for disease progression or death, 0.77; 95% CI, 0.63−0.95; P = .02).

Atezolizumab. IMpower133 (NCT02763579), a double-blind, placebo-controlled, randomized, phase III trial, compared four cycles of carboplatin and etoposide with either atezolizumab (n = 201) or placebo (n = 202), followed by maintenance with either atezolizumab or placebo (as per the original randomization) until unacceptable toxic effects, disease progression, or no additional benefit.[2]

The toxicity event rate was similar for both arms, consistent with known adverse events of the individual agents. Grade 3 or 4 adverse events occurred in 56.6% of patients in the atezolizumab group and 56.1% of patients in the placebo group.

Durvalumab. CASPIAN (NCT03043872) was a randomized, open-label, phase III trial that assigned patients to durvalumab plus platinum-etoposide (n = 268), durvalumab plus tremelimumab (a cytotoxic T lymphocyte antigen-4 [CTLA-4] inhibitor) plus platinum-etoposide (n = 268), or platinum-etoposide alone (n = 269). In the immunotherapy arms, patients received four cycles of platinum-etoposide plus durvalumab with or without tremelimumab, followed by durvalumab maintenance until intolerance or disease progression or until other discontinuation criteria were met. In the chemotherapy-alone arm, up to six cycles of chemotherapy could be given, as well as PCI, at the investigator’s discretion. At the time of planned interim OS analysis, the durvalumab plus platinum-etoposide group met the predefined threshold for statistical significance.[3]

Durvalumab. CASPIAN (NCT03043872) was a randomized, open-label, phase III trial that assigned patients to durvalumab plus platinum-etoposide (n = 268), durvalumab plus tremelimumab (a cytotoxic T lymphocyte antigen-4 [CTLA-4] inhibitor) plus platinum-etoposide (n = 268), or platinum-etoposide alone (n = 269). In the immunotherapy arms, patients received four cycles of platinum-etoposide plus durvalumab with or without tremelimumab, followed by durvalumab maintenance until intolerance or disease progression or until other discontinuation criteria were met. In the chemotherapy-alone arm, up to six cycles of chemotherapy could be given, as well as PCI, at the investigator’s discretion. At the time of planned interim OS analysis, the durvalumab plus platinum-etoposide group met the predefined threshold for statistical significance.[3]

The median OS was 12.9 months in the durvalumab plus platinum-etoposide group versus 10.5 months in the platinum-etoposide group (HR for OS, 0.75; 95% CI, 0.62−0.91; nominal P = .0032).[3][Level of evidence A1]

Durvalumab. CASPIAN (NCT03043872) was a randomized, open-label, phase III trial that assigned patients to durvalumab plus platinum-etoposide (n = 268), durvalumab plus tremelimumab (a cytotoxic T lymphocyte antigen-4 [CTLA-4] inhibitor) plus platinum-etoposide (n = 268), or platinum-etoposide alone (n = 269). In the immunotherapy arms, patients received four cycles of platinum-etoposide plus durvalumab with or without tremelimumab, followed by durvalumab maintenance until intolerance or disease progression or until other discontinuation criteria were met. In the chemotherapy-alone arm, up to six cycles of chemotherapy could be given, as well as PCI, at the investigator’s discretion. At the time of planned interim OS analysis, the durvalumab plus platinum-etoposide group met the predefined threshold for statistical significance.[3]

The toxicity event rate was similar in both arms, consistent with known adverse events of the individual agents. Grade 3 or 4 events occurred in 62% of patients in both study arms.