Long-term ES-SCLC outcomes on durvalumab–chemotherapy predicted by PFS duration
medwireNews: A progression-free survival (PFS) of at least 12 months is a strong indicator of good survival outcomes at 2 years in patients with extensive-stage small-cell lung cancer (ES-SCLC) taking durvalumab alongside first-line platinum–etoposide, even in those with poor prognostic factors, analysis of CASPIAN data shows.
In total, 17.0% of 265 patients in the CASPIAN trial taking durvalumab plus platinum–etoposide had PFS lasting 12 months or more, as did 16.4% of the 531 patients combining those who took durvalumab and chemotherapy with or without tremelimumab, as well as 4.5% of the 266 who received only chemotherapy.
At the ESMO Virtual Congress 2020, presenting author Jonathan Goldman (David Geffen School of Medicine, Los Angeles, California, USA) explained that patients across all arms who had PFS lasting for a minimum of 12 months were numerically, albeit not significantly, less likely to have poor prognostic characteristics, such as brain and liver metastases, and more likely to have a low WHO performance score of 0.
And tissue tumor mutational burden (TMB), data on which were available for 283 patients, was not significantly associated with rates of long-term benefit in any of the treatment regimens. Therefore, Goldman said that “neither TMB nor clinical characteristics appear to identify patients who derive long-term benefit.”
However, Goldman highlighted “exceptional” 2-year overall survival (OS) rates across the treatment arms in those with PFS of at least 12 months, at 76.7%, 82.2%, and 83.3% for those in the durvalumab plus chemotherapy, the combined durvalumab, and chemotherapy alone groups. By comparison, 2-year OS rates ranged from 10.4% to 11.1% in patients with a PFS shorter than 12 months.
Patients with PFS of 12 months or more also had higher confirmed objective response rates (94 to 100% vs 57 to 63%) and better median duration of response and depth of response, and at data cutoff after a median follow-up of 2 years, around half of patients with a PFS of at least 12 months were still responding, compared with no patients with a shorter PFS.
Despite durvalumab-treated patients with a PFS of at least 12 months experiencing a greater number of immune-mediated adverse events (AEs), Goldman noted that the number of grade 3–4 AEs, serious AEs, and AEs leading to discontinuation were comparable to those in the patients with a shorter PFS.
Goldman concluded that “[f]urther investigation into predictive factors for long-term benefit with durvalumab is ongoing.”
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