Dr Haggstrom on Future Research Directions in EGFR+ and ALK+ NSCLC

Daniel E. Haggstrom, MD, Hematology, Medical Oncology (Cancer), Atrium Health Levine Cancer Institute, discusses future research directions engendered by prior studies within EGFR-and ALK-mutant non–small cell lung cancer (NSCLC).

For patients with EGFR-mutant NSCLC, the established efficacy of treatment with osimertinib (Tagrisso) as a targeted therapeutic option has driven research towards investigating combination regimens in the metastatic setting, Haggstrom begins. Phase 3 trials such as FLAURA2 (NCT04035486), which combined chemotherapy with osimertinib, and the MARIPOSA study (NCT04487080), which investigated the combination of lazertinib (Lazcluze) with amivantamab-vmjw (Rybrevant), are examining the potential to improve patient outcomes further, he notes. As these data mature, they will inform next steps, particularly for patients who are fit enough to undergo combination treatments, Haggstrom says. The MARIPOSA trial also includes an arm comparing lazertinib monotherapy with osimertinib, making the eventual head-to-head data release between lazertinib and osimertinib highly anticipated, Haggstrom states.

In the ALK-positive NSCLC setting, alectinib (Alecensa) remains a preferred first-line choice, largely due to its favorable toxicity profile, as shown in the phase 3 ALTA-3 trial (NCT03596866), Haggstrom continues. However, lorlatinib (Lorbrena) may challenge this standard in the future, as it has demonstrated a longer progression-free survival (PFS) at the 60-month mark compared with alectinib or brigatinib (Alunbrig), he reports. Importantly, ALK-targeted therapies are now being evaluated in earlier-stage, resected lung cancer as well, Haggstrom says. The phase 3 ALINA trial (NCT03456076) has explored alectinib’s use in an adjuvant setting for patients with resected, ALK-positive disease. Similar to that of EGFR-driven NSCLC, these trials indicate that targeted therapies are progressively moving into earlier disease stages, with the potential to improve long-term survival outcomes, Haggstrom underscores.

Alltogether, these trials underscore a strategic evolution toward using targeted agents in both metastatic and early-stage settings, potentially altering the treatment landscape across EGFR- and ALK-positive NSCLC, Haggstrom concludes.