Daily highlight in lung cancer

Reported by Prof Dr Demedts – AZ Delta Roeselare, Belgium

The FLAURA2 trial, where initial data unveiled at the World Lung Conference showed that integrating chemotherapy into the standard care for EGFR-mutated patients significantly enhanced progression-free survival (PFS) by approximately 30%. Notably, within this cohort, 40% of patients exhibited brain metastasis, forming the focus of this investigation. The study concentrated on patients treated with osimertinib alongside platinum-permetrexed (CTx), showing similar efficacy for both measurable and non-measurable brain lesions. Results unequivocally emphasized the advantage of combining chemotherapy with osimertinib, manifesting in reduced risks of CNS progression or mortality, heightened CNS ORR, elevated instances of CNS complete response, and enhanced durability of CNS response. In essence, the trial underscored the favorable outcomes achieved by incorporating chemotherapy into EGFR inhibitor therapy for the 40% of patient population with brain lesions.

Another area of exploration involved the addition of angiogenic inhibitors into the treatment backbone of EGFR inhibitors. Noteworthy were two trials examining the addition of ramucirumab to osimertinib for stage 4 lung cancer patients.

The OSIRAM-1 trial yielded negative results, demonstrating no significant difference in PFS and OS. Crucially, patient dropout and premature study termination stemmed from the rigorous four-month IV treatment cycle occurring biweekly, compounded by the severity of side effects and the challenges posed by the COVID pandemic.

In contrast, the RAMOSE trial, featuring IV administration of ramucirumab every three weeks, exhibited similar response rates but significantly improved PFS. Prevalent grade 3 side effects such as arterial hypertension and neutropenia were effectively managed.

Discrepancies between the trials could be ascribed to the higher exposure to ramucirumab and the involvement of investigator-led outcome assessments in the RAMOSE trial.

Lastly, the TROPION-Lung05 trial delved again into the domain of EGFR-mutated advanced or metastatic NSCLC patients who had undergone extensive prior treatments. Here, the investigational use of datopotamab deruxtecan (Dato-DXd) was explored in a single-arm trial, with the primary endpoint being the overall response rate (ORS). The ORS stood at 36% within this heavily pretreated patient cohort, indicating a commendable outcome. Furthermore, the treatment exhibited manageable side effects, predominantly falling within the grade 1-2 spectrum.

References:

David Planchard – FLAURA2: safety and CNS outcomes of first-line (1L) osimertinib (osi) ± chemotherapy (CTx) in EGFRm advanced NSCLC. ESMO 2023 – LBA68

Yoshiro Nakahara – OSIRAM-1: A multicenter, open label, randomized phase II study of osimertinib plus ramucirumab versus osimertinib alone as initial chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer (TORG1833). ESMO 2023 – LBA70

Xiuning Le – A Multi-Centre Open-Label Randomized Phase II Study of Osimertinib with and without Ramucirumab in TKI-naïve EGFR-mutant Metastatic NSCLC (RAMOSE trial interim analysis). ESMO 2023 – LBA71

Luis Paz-Ares – TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs). ESMO 2023 – 1314MO