PFS Predicts Long-Term Outcomes For CASPIAN Participants

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Exploratory analyses show that duration of progression-free survival (PFS) predicts overall survival (OS) of extensive-stage small-cell lung cancer (ES-SCLC) in patients participating in the CASPIAN trial. 

By contrast, tumour mutational burden (TMB) was not associated with OS in the study, reported Jonathan Goldman, from David Geffen School of Medicine at UCLA in the USA, at the ESMO Virtual Congress 2020. 

He presented the update on the phase III trial that previously demonstrated a significant improvement in OS after at least 2 years of follow-up for ES-SCLC patients given durvalumab plus platinum–etoposide (EP) versus the chemotherapy regimen alone. 

Tissue TMB findings were available for 35% of the intention-to-treat population of the study. But whether using a range of TMB cutoffs from 8–14 mutations/Mb or TMB as a continuous variable, the researchers found the biomarker did not predict OS in patients given durvalumab plus EP, those given durvalumab plus EP alongside tremelimumab or patients receiving EP alone, said Jonathan Goldman. 

When the durvalumab plus EP and the durvalumab–tremelimumab plus EP arms were combined into one group of 531 patients, a PFS of at least 12 months was achieved by 16.4% versus 4.5% of 266 patients given EP only.  

Analysis indicated that patients in the combined immunotherapy arm with PFS of at least 12 months had longer median use of durvalumab than those with a shorter PFS (25 vs 6 months) but there was no difference in EP exposure or baseline clinical characteristics between those who did and did not derive a longer PFS benefit. 

Patients in the combined immunotherapy plus EP arm with a PFS of at least 12 months had a higher objective response rate (ORR) than those with a shorter PFS (94 vs 58%), as well as a longer median duration of response (not reached versus 4 months) and a higher proportion remained in response over 6 and 24 months of follow-up (100–59% versus 20–0%). 

A PFS of 12 months or beyond was also associated with a greater depth of response in the combined immunotherapy plus EP arm, with a median best change in target lesion reduction of 74.59% versus 52.78% for those with a shorter duration. 

A similar pattern was also observed for the EP only group with regard to PFS duration and likelihood of ORR, duration of response, proportion of patients continuing with response at 6–24 months and depth of response. 

Moreover, a PFS of 12 months or longer significantly predicted improved OS for both patients in the combined immunotherapy plus EP and EP only arms, with median OS unreached in both groups versus 10.1 and 10.0 months for the two arms, respectively, among patients with a PFS of less than 12 months.  

This was reflected in the 24-month OS rates, with respective rates of 82.2% and 83.3% for the patients with extended PFS who received immunotherapy plus EP and EP alone, but corresponding rates of 11.0% and 10.4% for patients with a shorter PFS. 

The presenter noted that grade 3–4 treatment-related adverse events (AEs), serious AEs and AEs leading to discontinuation were “similar” in those with and without a PFS of 12 months, despite patients with PFS of at least 12 months having greater durvalumab exposure and a numerically higher rate of immune-related AEs.  

“In summary, there were three times more patients deriving long-term benefit when treated with durvalumab plus EP versus EP alone in the CASPIAN trial”, the presenter concluded. 

But patients in all treatment arms with PFS of at least 12 months had better outcomes, including “exceptional” 2-year rates of over 75%, Jonathan Goldman said, adding that “further investigation into predictive factors for long-term benefit with durvalumab is ongoing.” 

Reference  

Goldman JW, Garassino MC, Chen Y, et al. Durvalumab (D) ± platinum-etoposide (EP) in 1L ES-SCLC: Characterization of long-term clinical benefit and tumour mutational burden (TMB) in CASPIAN. Ann Oncol 2020; 31 (Suppl 4): S1142–S1215. DOI: 10.1016/annonc/annonc325