Immunotherapy: a new era in small-cell lung cancer

• Published in: The Lancet (British edition) 2019-11, Vol.394 (10212), p.1884-1885
• Main Author: Goetze, Thorsten Oliver
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal; Anticancer properties; Apoptosis; Brain cancer; Cancer immunotherapy; Cancer therapies; Carboplatin; Cell death; Chemoradiotherapy; Chemotherapy; Cisplatin; Clinical trials; Etoposide; Fatalities; Humans; Immune checkpoint inhibitors; Immune system; Immunotherapy; Lung cancer; Lung Neoplasms; Medical prognosis; Metastases; Metastasis; Monoclonal antibodies; Non-small cell lung carcinoma; Patients; PD-L1 protein; Platinum; Regulators; Survival; Targeted cancer therapy; Tumors
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(19)32235-4

Lung cancer is the most frequently diagnosed cancer (11·6% of all cancer cases) and the leading cause of deaths due to cancer (18·4% of all cancer deaths).1 About 15% of all diagnosed lung cancers are small-cell lung cancer (SCLC) and up to 60–70% of these are extensive-stage SCLC (ES-SCLC) at initial diagnosis.2,3 The standard-of-care treatment for ES-SCLC in the past two decades was chemotherapy consisting of carboplatin or cisplatin, combined with etoposide.4–6 Despite response rates of 60–65% for ES-SCLC, prognosis rarely exceeds 10 months.6,7 Caused by a high tumour mutational burden, SCLC is a good candidate for immune-checkpoint inhibition therapy. Immunecheckpoint inhibition is a form of anti-cancer immunotherapy that targets key regulators of the immune system.8–10 In early-phase clinical trials, durvalumab, which targets the programmed cell death ligand 1 (PD-L1), has already shown safety and antitumour activity in patients with pretreated ES-SCLC.11,12 Among patients with stage III, unresectable non-small-cell lung cancer after chemoradiotherapy, durvalumab has already been implemented as standard therapy.13 The randomised phase 3 IMpower133 trial14 has shown that the addition of the PD-L1 checkpoint inhibitor atezolizumab to carboplatin and etoposide during first-line treatment of ES-SCLC resulted in significant improvement in overall survival and progression-free survival compared with chemotherapy alone. For the 35 patients with brain metastases in the IMpower133 trial,14 overall or progression-free survival was not different between the two treatment groups; for the 55 patients with cerebral seeding in the CASPIAN trial,15 the addition of durvalumab led to an improvement versus platinum–etoposide alone (hazard ratio 0·69 [95% CI 0·35–1·31]).