Treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC) has moved beyond a single standard approach. In the past, most patients received osimertinib alone. Now, doctors choose between single-drug therapy and stronger combination treatments based on the patient’s condition and cancer behavior.
Osimertinib (brand name Tagrisso) remains an important option, especially for patients with lower-risk disease who need a well-tolerated treatment. In the FLAURA study, osimertinib showed good effectiveness with manageable side effects.
However, newer studies have changed practice. The FLAURA2 trial tested osimertinib combined with platinum chemotherapy and pemetrexed. This combination improved progression-free survival and overall survival compared to osimertinib alone. It was especially helpful for patients with brain metastases or high tumor burden.
Another major study, MARIPOSA, evaluated a chemotherapy-free combination: amivantamab plus lazertinib. This dual-targeted approach also improved overall survival and extended response duration compared to osimertinib alone. However, it requires intravenous infusions and careful management of side effects such as low albumin levels and skin reactions.
In 2026, doctors consider three main factors when choosing initial treatment:
The patient’s overall health and ability to tolerate therapy.
How aggressive or widespread the cancer is.
The expected side effects of each option.
Using stronger combination therapy upfront can control disease earlier, but it may limit future treatment options. If chemotherapy is used first, it cannot be reused later. As a result, second-line treatment strategies are evolving. Options now include antibody-drug conjugates such as Datopotamab deruxtecan, bispecific antibodies like Ivonescimab, and MET-targeted therapies for specific resistance mutations.
Overall, treatment decisions are no longer about choosing a single “best” drug. Instead, doctors design a long-term plan that balances early disease control with quality of life and future treatment opportunities.