Update on the Biology, Management, and Treatment of Small Cell Lung Cancer

About this Research Topic

Background

Small cell lung cancer (SCLC) accounts for 10-15% of newly diagnosed cases of lung cancer. The majority of patients with SCLC present with extensive stage (ES) disease at the time of diagnosis. Standard first-line treatment for patients with ES SCLC is palliative chemotherapy with 4-6 cycles of a platinum-etoposide doublet. SCLC is very responsive to initial chemotherapy; however, most patients relapse or progress after treatment, and there are limited therapeutic options beyond first-line therapy. The prognosis for patients with SCLC is extremely poor with 5-year survival ranging from 2-31% depending on the disease stage. There is an unmet need for the development of more effective and less toxic therapy for patients with SCLC, especially for patients with disease progression after frontline platinum-based regimens.

Immune checkpoint inhibitors, specifically PD-1/PD-L1 inhibitors are being actively evaluated as a treatment strategy in SCLC. Initial studies show that treatment with a single agent immune checkpoint inhibition has limited efficacy in this patient population with a response rate of 15-20% in previously treated small cell lung cancer. The combination of nivolumab and ipilimumab shows an improvement in response rate compared to nivolumab alone but is associated with higher toxicity. Recently, treatment with a combination of PD-L1 inhibitor, atezolizumab, and etoposide-based chemotherapy has shown a survival advantage over chemotherapy alone in first-line treatment of SCLC. These advances in immunotherapy strategies for SCLC have been incorporated into the NCCN guidelines. Furthermore, a substantial amount of genetic and cellular intratumor heterogeneity in SCLC has been identified. In addition to a loss of function of the RB and TP53 gene in the majority of tumors, there has been recent identification of several potentially targetable mutations in SCLC with therapeutic implications.

This Research Topic aims to provide a comprehensive source of articles describing recent advances in therapy for SCLC, the biology of SCLC and ongoing studies that will shape the future treatment of patients with SCLC. We welcome Original Research or Review articles, focused on the following topics:

1) Evolving treatment strategies in SCLC including the role of immunotherapy, targeted therapy ( for example inhibitors of DLL-3, BLC-2, IGF1R, PARP, CHK1 or AURA A and AURA B), antibody drug conjugates/chemotherapy and radiation therapy in the treatment of limited stage and extensive stage SCLC.
2) Current understanding of the signaling pathways in SCLC.
3) Emerging biomarkers of response to therapy in SCLC patient population.

JG declared honoraria from AstraZeneca, Celgene, Takeda, Janssen, Genentech, Eli Lilly, Triptych Health Partners; consulting or advisory role to AstraZeneca, Janssen, Genentech, Eli Lilly, Celgene, Takeda, Triptych Health Partners; and research funding from AstraZeneca, Array, Merck, Epic Sciences, Genentech, BMS, BI, Trovagene, Loxo, Blueprint, Novartis. NL declared institutional funding from Array, Guardant (Pending – Merck, Pfizer); honoraria for independent CME – AZ, BMS, MSD, Roche, Pfizer; consulting (compensated) – Canadian Agency of Drugs and Technologies in Health and advisory role (uncompensated) – AZ, BMS, MSD, Roche, Pfizer, Novartis, Lilly, Nektar. BL is an employee of the Princess Margaret Cancer Center- University Health Network and declared equity (Stocks totaling <$2.500) with Pfizer.

Keywords: Small cell lung cancer, immunotherapy, targeted therapy, biomarkers

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