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 

-mutant non–small cell lung cancer (NSCLC).

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.

-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, 

-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 

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Daniel E. Haggstrom, MD, discusses future research directions within EGFR-and ALK-mutant non–small cell lung cancer.

Dr Haggstrom on the Role of Osimertinib in Unresectable EGFR-Mutated NSCLC

Daniel E. Haggstrom, MD, Hematology, Medical Oncology (Cancer), Atrium Health Levine Cancer Institute, discusses the role of osimertinib (Tagrisso) in the treatment of unresectable 

-mutated non-small cell lung cancer (NSCLC) following the phase 3 LAURA trial (NCT03521154).

the FDA approved treatment with osimertinib for adult patients with locally advanced, unresectable, stage III NSCLC

. These were patients whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have 

 exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Furthermore, this regulatory decision was supported by data from the LAURA.

The LAURA trial represents the first successful integration of targeted therapy into the stage III space for 

-mutated NSCLC, Haggstrom begins. Patients who completed chemoradiation therapy and achieved a confirmed response were randomized to receive either osimertinib, an EGFR TKI, or placebo. Progression-free survival (PFS) served as the primary end point of the investigation. 

 showed that patients treated with osimertinib (n = 143) had a median PFS of 39.1 months (95% CI, 31.5–not estimable) compared with 5.6 months (95% CI, 3.7-7.4) in the placebo group (n = 73; HR, 0.16; 95% CI, 0.10-0.24; 

 < .001). This improvement underscores osimertinib’s efficacy in controlling NSCLC in this patient population, Haggstrom emphasizes.

The trial also indicated a potential trend toward improved overall survival (OS) with osimertinib, though OS data remain immature due to a high crossover rate from placebo to active treatment, Haggstrom continues. The therapy's manageable toxicity and PFS benefits led to a shift in the standard of care for this patient population, Haggstrom explained. Safety and tolerability of osimertinib were consistent with its known profile, with toxicity levels manageable even in patients who had undergone intensive chemoradiation therapy.

The LAURA trial underscores the evolving role of targeted therapy in earlier-stage NSCLC and its potential to improve outcomes where immunotherapy may be less effective, Haggstrom concludes.

Daniel E. Haggstrom, MD discusses the role of osimertinib for patients with unresectable EGFR-mutated non-small cell lung cancer.

Daniel E. Haggstrom, MD

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

Dr Haggstrom on the Role of Osimertinib in Unresectable EGFR-Mutated NSCLC