The past decade has seen significant advancements in the treatment of small cell lung cancer (SCLC). The improvement in such areas as genomic profiling, diagnostics, and therapeutics can be linked, in part, to the Recalcitrant Cancer Research Act of 2012, which required the US National Cancer Institute (NCI) to identify two types of recalcitrant cancers that cause the death of at least 30,000 patients in the US per year and with a 5-year survival rate of less than 20%.
That mandate led to the formation a scientific framework to combat SCLC and to the formation of the NCI’s SCLC Consortium. Professor Charles M. Rudin, MD, PhD, who helped lead the NCI’s SCLC initiative, reviewed the progress made during the past decade and discussed the most pressing challenges ahead during the closing keynote address at the IASLC 2023 Hot Topic Meeting: Small Cell Lung Cancer.
Dr. Rudin, who is Chief of Thoracic Oncology at Memorial Sloan Kettering Cancer Center, New York, said the NCI’s efforts have facilitated increased information access and exchange as well as collaboration among members of the SCLC Consortium.
“I think the NCI SCLC Consortium really has had a major impact on small cell research,” Dr. Rudin said. “Not only in this country, but because we all work on an international stage, I think this initiative has primed the pump for SCLC research pretty broadly.”
The SCLC Consortium was tasked with identifying the five most pressing needs for progress against SCLC in 2013. The group published a white paper that called for better research tools, comprehensive genomic profiling, new diagnostic approaches, therapeutic development efforts, and the analysis of mechanisms of acquired drug- and radio-resistance. Dr. Rudin cited improvements related to each targeted initiative in the decade since the paper was published.
“These all remain needs today, but I think we have made progress,” he said.
Dr. Rudin also celebrated the impact of immunotherapy for SCLC patients. With about 10% of patients exhibiting positive response rates, the 3-year survival rate among this population has tripled, according to recent data.1 He noted there are now durable survivors of SCLC, due in large part to immunotherapy, but he acknowledged that there is still a long way to go with the treatment.
“Figuring out what we can do about the other 90% to actually get them to respond to immunotherapy, to me, is the big challenge in the field,” he said.
While there is no consensus on a strategy to raise the tail of the survival curve for extensive-stage SCLC, there are several therapeutic options that signal reasons for optimism. Dr. Rudin cited the durability of response rates to tarlatamab, pre-clinical data related to DNA damage response inhibitors to activate stimulator of interferon genes (STING), and the promising developments of epigenetic priming as potential solutions to improve the overall survival curve.
He acknowledged that several noteworthy new priorities had emerged since the publication of the SCLC Consortium’s white paper in 2013. Despite significant progress, Dr. Rudin said that the field seemed to understand even less about the micro-environment of tumors, specifically the immune milieu, than ever before. He proposed integrating more immunologists into SCLC research and discussions to address the knowledge gap. He also cited the inability of researchers to mimic brain metastases caused by SCLC with mouse models as another challenge that must be expediently addressed.
References
- 1. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. doi:10.1016/j.esmoop.2022.100408
