FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer

Abstract

The U.S. Food and Drug Administration (FDA) granted approval to atezolizumab and durvalumab in March of 2019 and 2020, respectively, for use in combination with chemotherapy for first-line treatment of patients with extensive stage small cell lung cancer. These approvals were based on data from two randomized controlled trials, IMpower133 (atezolizumab) and CASPIAN (durvalumab). Both trials demonstrated an improvement in overall survival (OS) with anti-PD-L1 antibodies when added to platinum-based chemotherapy as compared to chemotherapy alone. In IMpower133, patients receiving atezolizumab with etoposide and carboplatin demonstrated improved OS (HR 0.70; 95% CI: 0.54, 0.91; p=0.0069) with median OS of 12.3 months compared to 10.3 months in patients receiving etoposide and carboplatin. In CASPIAN, patients receiving durvalumab with etoposide and either cisplatin or carboplatin also demonstrated improved OS (HR 0.73; 95% CI: 0.59, 0.91; p=0.0047) with median OS of 13.0 months compared to 10.3 months in patients receiving etoposide and either cisplatin or carboplatin. The safety profiles of both drugs were generally consistent with known toxicities of immune-checkpoint inhibitor therapies. This review summarizes the FDA perspective and data supporting the approval of these two agents. The Oncologist 2021;9999:• • Implications for Practice: Effective therapeutic options for small cell lung cancer (SCLC) are limited and there has been modest improvement in the overall survival (OS) of SCLC patients over the past three decades [1]. The approvals of atezolizumab and of durvalumab in combination with chemotherapy for first-line treatment of patients with extensive stage SCLC represent the first approved therapies for this patient population with OS benefit since the approval of etoposide in combination with other approved chemotherapeutic agents. Additionally, the efficacy results from IMpower133 and CASPIAN lay the groundwork for possible further evaluation in other treatment settings in this disease.

Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

“…The NCCN SCLC Panel recommends (category 1) durvalumab plus etoposide plus (carboplatin or cisplatin) as a preferred firstline systemic therapy option followed by maintenance durvalumab for patients with extensive-stage SCLC based on clinical trial data and the FDA approval (see SCL-E 1, page 1450). 86,[89][90][91] Other Primary Systemic Therapies Other recommended regimens for extensive-stage SCLC include etoposide with either cisplatin or carboplatin (see SCL-E 1, page 1450). Before the recent favorable data on immunotherapy, many other chemotherapy combination regimens had been evaluated in patients with extensive-stage disease with little consistent evidence of benefit compared with EP.…”

Absence of Biomarker-Driven Treatment Options in Small Cell Lung Cancer, and Selected Preclinical Candidates for Next Generation Combination Therapies

“…The CASPIAN study tested another PD-L1 inhibitor, durvalumab, in combination with etoposide and platinum. In this study, there was statistical benefit to adding durvalumab to first-line treatment, with patients receiving durvalumab, etoposide and platinum achieving an overall survival of 13.0 months compared to 10.3 months in the control arm (Mathieu et al, 2021). In March 2020, the US FDA approved durvalumab in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer.…”

“…Atezolizumab, when added to first line carboplatin and etoposide, improves overall survival. The IMpower33 study showed that patients receiving atezolizumab, carboplatin and etoposide had a median overall survival of 12.3 months compared to 10.3 months in the control group ( Mathieu et al, 2021 ). Progression free survival was also statistically improved, with a PFS of 5.2 months in the experimental arm compared to 4.3 months in the control arm ( Mathieu et al, 2021 ).…”

“…The IMpower33 study showed that patients receiving atezolizumab, carboplatin and etoposide had a median overall survival of 12.3 months compared to 10.3 months in the control group ( Mathieu et al, 2021 ). Progression free survival was also statistically improved, with a PFS of 5.2 months in the experimental arm compared to 4.3 months in the control arm ( Mathieu et al, 2021 ). In March 2019, the US FDA approved atezolizumab in combination with carboplatin and etoposide for the first-line treatment of patients with extensive-stage small cell lung cancer.…”

Malignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity?

“…In addition, complete tumor regression has been observed in some NSCLC (20)(21)(22) and SCLC (23)(24)(25) patients treated with chemo-immunotherapy. Atezolizumab and durvalumab are also approved in combination with platinum-based chemotherapy for advanced SCLC patients (26). However, these best-case responses are only observed in a minority of patients.…”