Editor’s note: From September 13 to 17, the 2024 ESMO Annual Meeting is in full swing in Barcelona, Spain. Oncology Frontier is attending the event and bringing you first-hand insights from the conference. During the non-metastatic non-small cell lung cancer (NSCLC) paper session held on September 13, Dr. Suresh Senan from Amsterdam, Netherlands, presented the latest results from the ADRIATIC study, where subgroup analysis further supports previous practice-changing findings.

The first interim analysis of the ADRIATIC study revealed significant improvements in both overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed after concurrent chemoradiotherapy, when treated with durvalumab consolidation therapy compared to placebo (J Clin Oncol. 2024;42(Suppl):LBA5). The new subgroup analysis presented at the 2024 ESMO meeting supports the use of immunotherapy regardless of whether patients had previously received concurrent chemoradiotherapy or prophylactic cranial irradiation (PCI; LBA81).

For patients who had undergone PCI (‘PCI-yes’; n=285), the median OS was not reached (NR) in the durvalumab group, compared to 42.5 months in the placebo group (hazard ratio [HR] 0.75). Among those who had not received PCI (‘PCI-no’; n=245), the median OS was 37.3 months and 24.1 months for the durvalumab and placebo groups, respectively (HR 0.71). Across both PCI and non-PCI groups, PFS was longer in the durvalumab group compared to placebo. For PCI recipients, the median PFS was 28.2 months versus 13.0 months (HR 0.73), and for non-PCI patients, it was 9.1 months versus 7.4 months (HR 0.80).

Additionally, a subgroup analysis based on radiotherapy dosing frequency (twice daily [BID; n=148] versus once daily [QD; n=382]) demonstrated that OS and PFS were superior in the durvalumab group, regardless of the radiotherapy regimen, with longer duration of benefit observed in those who received BID radiotherapy. A separate subgroup analysis of chemotherapy type (carboplatin [n=179] or cisplatin [n=351]) also showed that durvalumab outperformed placebo in both OS and PFS, across both chemotherapy groups.

The incidence of grade 3-4 treatment-emergent adverse events (TEAEs) was similarly high in both the durvalumab and placebo groups across all subgroups. In the PCI subgroup, it was 28.4% versus 29.6%, and in the non-PCI subgroup, it was 19.8% versus 17.9%. For those who received carboplatin, it was 31.5% versus 31.8%, and for cisplatin, 20.8% versus 20.3%. The rate of TEAEs leading to discontinuation of durvalumab was similar across all subgroups. No significant safety differences were found between the BID and QD radiotherapy groups.

Dr. Stephen Liu from Georgetown University, Washington, DC, noted that subtle differences could be observed between subgroups in the analysis. For example, patients who received PCI, regardless of the treatment group, had longer absolute OS and PFS than those who did not receive PCI. Additionally, BID radiotherapy was associated with improved absolute survival compared to QD radiotherapy. However, Liu emphasized that “there are some issues with these comparisons since PCI is typically given to fitter, stronger patients, and the same goes for BID versus QD radiotherapy. Many confounding factors must be considered, as baseline characteristics were not balanced, and patients in the better-performing groups had better baseline characteristics.”

Dr. Liu also pointed out that a multivariate analysis, which adjusted for patient characteristics and differences in PCI and concurrent chemoradiotherapy, revealed no significant interactions. He added, “The durvalumab regimen shows an impressive safety profile, and given that treatment is delivered after radiotherapy, the toxicity data are reassuring.” Liu concluded by stressing the importance of these findings for the future treatment of LS-SCLC, stating, “The goal of standard chemoradiotherapy is curative intent, which is ambitious. From the control group, we can see that most people are not cured. However, these data bring the possibility of curing more LS-SCLC patients, and this has immediately changed practice—every patient should benefit from this.”

Reference

Senan S, et al. 度伐利尤单抗 (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): Outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial. ESMO Congress 2024, LBA81