Dr Halmos on Combination Strategies and Expanding Options in EGFR-Mutant NSCLC

“Combination treatments are [now] the most strongly recommended frontline [approach] for patients with advanced EGFR-mutated lung cancer. [It’s] nice to have 2 different combinations to tailor that to the patient in front of us.”

Balazs Halmos, MD, a professor in the Department of Oncology and the Department of Medicine at Albert Einstein College of Medicine, associate director of clinical science at the Montefiore Einstein Comprehensive Cancer Center, discussed how combination regimens have reshaped frontline treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC), later-line options, and quality of life at the 21st Annual New York Lung Cancers Symposium.

Combination therapies can do a better job of extending progression-free survival (PFS) and overall survival (OS), Halmos said, citing osimertinib (Tagrisso) plus chemotherapy from the phase 3 FLAURA2 trial (NCT04035486) and amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) from the phase 3 MARIPOSA trial (NCT04487080). Although not every patient may be a candidate, combinations should be the more common approach, he noted.

Frontline combinations have also reshuffled second-line options, Halmos explained. The phase 3 SAFFRON trial (NCT05261399) informed precision medicine approaches with EGFR/MET combinations for MET amplification–positive disease in the second line and beyond, he added. Antibody-drug conjugates are also making a difference, according to Halmos, with a datopotamab deruxtecan now approved and sacituzumab govitecan (Trodelvy) showing improvements in PFS and OS compared with doublet chemotherapy in this setting.

These choices are better for patients but more complex for clinicians, Halmos said, underscoring the value of meetings such as the New York Lung Cancers Symposium for determining how to incorporate new advances.

Quality of life is critical, Halmos emphasized; since more intensive combinations will adversely affect it to some extent, clinicians must understand how to mitigate adverse effects so that extended survival is valuable. He described amivantamab plus lazertinib as a complicated regimen but noted that the field has learned how to administer it more safely and conveniently since its introduction, including through a subcutaneous formulation of amivantamab, dermatologic prophylaxis, and better management of thromboembolic events. Once an OS benefit is achieved, the field works to deliver it safely and with the highest possible quality of life, he concluded.