Imfinzi Continuously Demonstrates Survival Benefit in Limited Stage SCLC

Patients with limited-stage (cancer that is only on one side of the chest) small cell lung cancer (LS-SCLC) experienced improvements in both overall survival (OS; the time a patient lives regardless of disease status) and progression-free survival (the time a patient lives without their disease spreading or worsening) when treated with Imfinzi (durvalumab) compared with placebo.

These improvements were seen across subgroups based on factors associated with prior prophylactic cranial irradiation (PCI; radiation to the head to reduce the risk of cancer spreading to the brain, according to the National Cancer Institute) and concurrent chemoradiotherapy (CRT; chemotherapy administered at the same time as radiation) use, according to findings from the phase 3 ADRIATIC trial presented at the 2024 European Society for Medical Oncology Congress.

Regarding patients with prior PCI in the Imfinzi (142 patients) and placebo arms (143 patients), the median OS was not reached (meaning more than half of the patients in that arm were still alive) and 42.5 months, respectively. The 36-month OS rates were 62.1% versus 56.5%, respectively. Among patients who had no prior PCI in the Imfinzi (122 patients) and placebo arms (123 patients), data showed a median OS of 37.3 months and 24.1 months in each arm. After three years, the OS rates were 50.2% with Imfinzi versus 37.3% with placebo.

Among patients with prior PCI in the Imfinzi and placebo arms, the median PFS was 28.2 months versus 13 months, respectively. The 24-month PFS rates in each group were 54.6% and 38.5%. Among those without prior PCI, the median PFS was 9.1 months versus 7.4 months in each arm. At two years, the PFS rates were 37.1% versus 29.3% in each arm.

Among those who received carboplatin chemotherapy in the Imfinzi (91 patients) and placebo arms (88 patients), the median OS was not reached and 33.4 months in each arm. At three years, OS rates were 65.3% versus 46.7% in each arm.

Regarding patients who received cisplatin chemotherapy in the Imfinzi (173 patients) and placebo arms (178 patients), the median OS was 41.9 months versus 34.3 months in each arm. The three-year OS rates were 52.1% and 48.1%, respectively.

Regarding PFS in the carboplatin subgroups, the median PFS was 27.9 months in the Imfinzi arm versus 9.2 months in the placebo arm. At two years, the PFS rates were 54.8% versus 33.2%, respectively.

Among patients who received cisplatin, the median PFS was 11.4 months versus 9.7 months in each arm. The two-year PFS rates were 41.8% with Imfinzi and 34.8% with placebo.

Among patients who received 45 Gy of radiation twice daily over three weeks in the Imfinzi (69 patients) and placebo (79 patients) arms, the median OS was not reached versus 44.8 months in each group. The three-year OS rates were 65.8% vs 57.4% with Imfinzi and placebo, respectively.

Regarding those who received radiotherapy at 60 to 66 Gy once daily for six weeks in the Imfinzi (195 patients) and placebo arms (187 patients), the median OS was 41.9 months versus 26.1 months, respectively. At three years, the respective OS rates were 53.1% versus 43.3%.

In the twice-daily radiotherapy groups, the median PFS was 38.7 months with Imfinzi versus 14.3 months in the placebo arm. The two-year PFS rates were 60.5% versus 42.9% in each arm. Among patients who received once-daily radiotherapy, the median PFS was 11.4 months with Imfinzi versus 7.8 months with placebo. At two years, the PFS rates were 41% versus 30.3% with Imfinzi and placebo, respectively.

“The magnitude of benefit with [Imfinzi] versus placebo was consistent within the PCI and radiotherapy subgroups and varied somewhat between the chemotherapy subgroups. Multivariate analyses showed no significant interactions between [Imfinzi] treatment effect and PCI or concurrent [CRT] subgroups,” Suresh Senan, a professor of clinical experimental radiotherapy at the Amsterdam University Medical Centers (VUmc location) in The Netherlands, said in a presentation on these data. “[Imfinzi] demonstrated consistent benefit versus placebo irrespective of prior PCI use and concurrent [CRT] components, further supporting consolidation [Imfinzi] as the new standard of care in [LS-SCLC].”

In the ongoing, double-blind, international ADRIATIC trial, 730 patients with stage 1 to 3 LS-SCLC were randomly assigned to receive Imfinzi monotherapy (264 patients), placebo (266 patients), or Imfinzi plus Imjudo (tremelimumab, 200 patients). In this post hoc analysis of outcomes in the Imfinzi and placebo arms, investigators assessed PFS, OS and safety in prespecified subgroups based on prior PCI use and variables associated with concurrent CRT.

Of note, 35% and 34% of patients in the Imfinzi and placebo arms, respectively, were 65 years or older in the PCI subgroup compared with 45% and 45% in the non-PCI group. Additionally, most patients in each treatment arm received radiotherapy once daily in the PCI (66% versus 62%) and non-PCI groups (83% versus 80%). Additionally, a higher proportion of patients were 65 years and older in the carboplatin (49% versus 59%) subgroup compared with the cisplatin subgroup (34% versus 29%) and the intent-to-treat (ITT) population (39% vs 39%). Data also showed that more patients in the twice-daily radiotherapy group received PCI (70% versus 70%) compared with those in the once-daily radiotherapy subgroup (48% versus 47%) and the ITT population (54% versus 54%).

In terms of safety in the Imfinzi and placebo arms, respectively, the rate of grade 3 (severe)/4 (life-threatening) treatment-emergent side effects were higher in the PCI group (28.4% versus 29.6%) versus non-PCI group (19.8% versus 17.9%), higher in the carboplatin (31.5% versus 31.8%) versus cisplatin group (20.8% versus 20.3%) and higher in the once-daily radiation (26.4% versus 24.7%) versus the twice-daily radiation group (18.8% versus 22.8%).

Overall, rates of treatment-emergent side effects leading to treatment discontinuation were comparable across subgroups, and investigators reported no meaningful differences in safety outcomes across the once-daily and twice-daily radiotherapy groups.

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