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Ongoing Trials Explore Novel Combinations and Adjuvant Therapies in EGFR- and ALK-Mutant NSCLC

• The FLAURA2 and MARIPOSA phase 3 trials are evaluating the efficacy of osimertinib plus chemotherapy and lazertinib plus amivantamab, respectively, in metastatic EGFR-mutant NSCLC. • Lorlatinib may challenge alectinib as the preferred first-line treatment for ALK-positive NSCLC due to its longer progression-free survival. • Targeted therapies like alectinib are being investigated in earlier-stage, resected ALK-positive NSCLC, as shown in the phase 3 ALINA trial, to improve long-term survival. • Head-to-head data release between lazertinib and osimertinib is highly anticipated from the MARIPOSA trial.

Ongoing research is focused on refining treatment strategies for non-small cell lung cancer (NSCLC) harboring EGFR and ALK mutations, with trials investigating novel combinations and adjuvant therapies to improve patient outcomes. These studies aim to address unmet needs and optimize treatment approaches in both metastatic and early-stage settings.

Combination Therapies in EGFR-Mutant NSCLC

For patients with EGFR-mutant NSCLC, osimertinib has become a standard targeted therapy. Daniel E. Haggstrom, MD, of Atrium Health Levine Cancer Institute, highlights ongoing phase 3 trials exploring combination regimens to further enhance outcomes in the metastatic setting. The FLAURA2 trial (NCT04035486) is evaluating the combination of osimertinib with chemotherapy, while the MARIPOSA study (NCT04487080) is investigating the combination of lazertinib with amivantamab. "As these data mature, they will inform next steps, particularly for patients who are fit enough to undergo combination treatments," Dr. Haggstrom notes. The MARIPOSA trial also includes a lazertinib monotherapy arm compared with osimertinib, making the eventual head-to-head data release between lazertinib and osimertinib highly anticipated.

Evolving Treatment Landscape in ALK-Positive NSCLC

In the ALK-positive NSCLC setting, alectinib is currently favored as a first-line choice due to its favorable toxicity profile, as demonstrated in the phase 3 ALTA-3 trial (NCT03596866). However, lorlatinib may emerge as a strong contender, showing longer progression-free survival (PFS) at the 60-month mark compared with alectinib or brigatinib. Furthermore, ALK-targeted therapies are now being evaluated in earlier-stage, resected lung cancer. The phase 3 ALINA trial (NCT03456076) is exploring the use of alectinib in an adjuvant setting for patients with resected, ALK-positive disease. According to Dr. Haggstrom, these trials indicate a trend toward using targeted therapies in earlier disease stages, potentially improving long-term survival outcomes.

Strategic Shift Towards Targeted Agents

These trials collectively 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. The results from these studies are expected to refine treatment algorithms and improve outcomes for patients with these specific NSCLC subtypes.
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Reference News

[1]
Dr Haggstrom on Future Research Directions in EGFR+ and ALK+ NSCLC - OncLive
onclive.com · Nov 5, 2024

Daniel E. Haggstrom discusses future research in EGFR- and ALK-mutant NSCLC, focusing on combination therapies like osim...

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