Paul Bunn, MD, University of Colorado, presents during the first-ever US-based ESMO Series – 2022 ESMO Colorado.
At this year’s first-ever US ESMO Congress review session held in Denver, Colorado, Dr Paul Bunn from the University of Colorado discussed updates in small-cell lung cancer (SCLC), which usually represents a much smaller data set compared to the more common non-small cell lung cancer (NSCLC).
SCLC is typically found among smokers, and Dr Bunn first noted that, in older epidemiologic data from the US, the proportion of patients with no tobacco exposure (i.e., ‘never smokers’) diagnosed with SCLC was typically about 1%. Current data, however, show an increasing prevalence of SCLC among never-smokers. He noted for example, that data from 2 recent trials show a higher proportion of never smokers in their trial populations, roughly 3 to 7%. In addition, data from Asian clinical trial populations suggest a much higher incidence of never smokers with SCLC, approximately 20%. He noted that the reasons underlying the increase in SCLC among never smokers, while presumed to be related factors such as air pollution, are not entirely understood.
When comparing never smokers to current or former smokers with SCLC, Dr Bunn noted that never smokers with SCLC tend to be female, and also minorities, such that Black female never smokers have a higher risk for SCLC as compared with White women or male never smokers. Dr Bunn also noted that, whereas mutations in the p53 gene were more common in smokers relative to never smokers, mutations in the EGFR and PI3KCA genes were significantly more common among the never smokers. There was also a higher incidence of positive PD-L1 expression, an immune marker, among the never smokers, although this was not statistically significant. Dr Bunn suggested that, while not practice-changing at this time, the differences in the mutational landscape between smokers and never smokers with SCLC was interesting and worthy of continued study, especially in view of the increasing incidence of SCLC among never smokers.
With regard to updates in SCLC treatment, Dr Bunn outlined results from two major trials which examined the role of anti-PD-L1 immunotherapy, in combination with chemotherapy (etoposide-platinum), for patients with extensive-stage (ES) SCLC. In the 3-year update for the first trial, CASPIAN, patients on the immunotherapy durvalumab combined with chemotherapy had a median overall survival (OS) of 12.9 months, as compared with 10.5 months for those with chemotherapy alone, resulting in a statistically significant (P=0.0003), 29% relative reduction in the risk for death. While Dr Bunn noted that the median OS of roughly 13 months was not as impressive as compared with current NSCLC treatments, he emphasized that there still remain a sizable proportion of patients (~20%) who were alive after 3 to 4 years in this trial. This is an important finding, as it had been assumed that patients with ES-SCLC could not be cured, but the results show clearly that some of them can be. In the second trial, IMpower 133, the immunotherapy atezolizumab was given in combination with cisplatin/etoposide chemotherapy, as compared with chemotherapy alone. In this trial, there was a significant, 24% relative reduction in the risk of death for patients receiving atezolizumab as compared with chemotherapy alone, and the results showed a benefit of adding immunotherapy across all relevant patient subgroups. The results of these 2 trials, as Dr Bunn noted, clearly show that immunotherapy should be given (in combination with chemotherapy) to all patients with ES-SCLC, and regardless of their prior smoking status.
Dr Bunn also reviewed data from a dose-escalation study of a new antibody-drug conjugate compound, DS7300. This is an antibody directed against an immune target, B7-H3, that is expressed on many different cancer types, including SCLC. The antibody is fused to a cytotoxic drug called deruxtecan, and is designed to selectively kill cancer cells such as SCLC which express B7-H3 on the cell surface. The preliminary dose escalation study of DS7300, consisting primarily of patients in the US, but also Japan, included a total of 20 patients with SCLC. The results showed activity of DS7300 across several tumor types, including patients with SCLC, among whom a response rate of 58%, and a duration of response of 5.5 months was observed. The drug was generally well-tolerated with few patients discontinuing due to adverse events, and toxicities were as expected with predominantly chemotherapy-associated events such as nausea and anemia. The findings of the trial are supportive further development of DS7300 for SCLC and other cancers, and Dr Bunn noted this was one of the more exciting new drugs to presented at this year’s ESMO conference.
See more from the 2022 ESMO Colorado Conference here.
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