Recurrence patterns ADRIATIC

At the first planned interim analysis of the ongoing randomized, phase 3 ADRIATIC study, consolidation treatment with durvalumab was shown to significantly improve the dual primary endpoints of overall and progression-free survival, compared to placebo, in patients with limited stage small-cell lung cancer (LS-SCLC) without disease progression after concurrent chemoradiotherapy (cCRT). In this video, Prof Senan Suresh, radiation oncologist at the Amsterdam University Medical Center in Amsterdam, and Prof Mariana Brandão, medical oncologist at the Institut Jules Bordet in Brussels, discuss the updated results of this trial looking into the patterns of progression in both treatment arms.

For this analysis, progressions were classified as being intrathoracic (i.e., in the lung or mediastinum), or extrathoracic. In line with the previously reported survival data, consolidation durvalumab was shown to delay the occurence of both intrathoracic (median 37.3 vs. 26.6 months; HR[95%CI]: 0.82[0.61-1.09]) and extrathoracic (median not reached in both arms, HR[95%CI]: 0.67[0.49-0.93]) recurrences. Interestingly, the vast majority of extrathoracic recurrences involved a single organ. 

Given the importance of brain metastasis in patients with LS-SCLC, Prof Senan specifically zoomed in on central nervous system (CNS) recurrences. Consolidation durvalumab significantly delayed the development of CNS recurrences with a HR 0.64. At the 2-year landmark, this translated into an 11% absolute benefit in CNS-free survival for patients in the durvalumab arm. The ADRIATIC trial allowed prophylactic cranial irradiation (PCI), allowing the investigators to also assess the added benefit of this approach. Interestingly, the use of PCI reduced the incidence of CNS recurrences in both treatment arms, from 11.2% to 2.6% in the experimental arm and from 19% to 6.2% in the control arm. Based on these findings, Prof Senan is in favour of PCI in addition to consolidation durvalumab in younger, fit LS-SCLC patients. For older, less fit patients, there is an option to opt for vigilant CNS surveillance and the use of sterotactic radiotherapy in case of a CNS recurrence. This strategy seems reasonable given the solitary nature of most recurrences. In the years to come, the PRIMAlung study, evaluating brain MRI with or without PCI in patients with LS-SCLC, will hopefully shed more light on the optimal treatment strategy for these patients.