Dr. Chiang on Advancements in the Treatment and Characterization of SCLC

Anne Chiang, MD, PhD, associate professor, medical oncology, Yale School of Medicine, associate cancer center director, Clinical Initiatives, Smilow Cancer Hospital, Yale Cancer Center, discusses recent advancements in the biological understanding and treatment of small cell lung cancer (SCLC).

Improved knowledge of disease biology in SCLC has revealed the disease's heterogeneity. Accordingly, research efforts in this space have focused on leveraging differences in characterization to improve the use of targeted therapeutics in both the first and second line.

The phase 3 IMpower133 trial (NCT02763579) evaluated the efficacy and safety of adding the PD-L1 inhibitor atezolizumab (Tecentriq) to first-line treatment with carboplatin and etoposide in extensive-stage SCLC. In this trial, the regimen improved both progression-free survival and overall survival (OS) vs placebo plus chemotherapy. Moreover, the combination showed particular benefit in patients with the inflamed molecular subtype.

These data led to the FDA approval of frontline atezolizumab plus platinum chemotherapy for this population.

The FDA approval of lurbinectedin (Zepzelca) in the second-line setting also expanded the armamentarium for SCLC. The agent was approved for patients with metastatic SCLC who progressed on or after platinum-based chemotherapy based on the results from a phase 2 basket trial (NCT02454972). Lurbinectedin was found to produce a modest overall response rate, and demonstrated a tolerable safety profile.

Many of these advancements in SCLC were made possible by improved analysis of tumor tissue. As SCLC is not typically treated with a surgical approach, the lack of access to available tumor tissue significantly limited research in this space. Increased collaboration between interventionalists and researchers has allowed for pre- and on-treatment tumor biopsies to be obtained, and analyses of tumor microenvironments to be conducted. These developments helped expand treatment options in SCLC, and may lead to outcomes that are more consistent with that of non–small cell lung cancer, Chiang concludes.

Editor's Note: Dr Chiang reports serving as a consultant or on an advisory board for AstraZeneca, Genentech, Regeneron; she received research funding from Bristol Myers Squibb, AbbVie, Amgen and Genentech.