KEY TAKEAWAYS
- The phase 2 study assessed the safety of combining OSI with LCT for treating EGFR mutant NSCLC patients.
- The trial’s primary endpoint was PFS, and safety was secondary.
- The study confirmed that the combination of OSI with LCT was well-tolerated in EGFR-mutated metastatic NSCLC pts.
In the phase II study, patients (pts) with metastatic NSCLC who hadn’t been treated with tyrosine kinase inhibitors and had specific EGFR mutations or T790M resistance mutation post-initial treatment were given OSI for 6–12 weeks. Those without any progression as per RECIST 1.1 criteria were then divided into two groups: receiving only OSI or a combination of LCT and OSI until disease progression. The primary endpoint was progression-free survival (PFS), while safety was a secondary objective. Patients underwent evaluations every two months following CTCAE v4.0 guidelines. All adverse events (AEs) linked to the treatment, whether potential, likely, or definite, were reviewed.
Between 2018 and 2022, a total of 122 pts participated in a randomized study. The median age of the pts was 65, with a range of 30 to 88 years old. Of these pts, 63 received OSI alone, while 59 received OSI plus LCT. Among the pts who received LCT, 59% received RT alone, 29% received surgery alone, and 12% received both RT and surgery. After a median follow-up of 16 months, with a range of 2 to 49 months, no grade 4/5 AEs were reported. There was no significant difference in grade 3 AEs between the patients who received OSI alone and those who received OSI plus LCT, with 16% and 29% rates, respectively (p = 0.08).
For those on OSI alone, the prevalent grade 3 adverse events (AEs) were hyponatremia (4.8%), transaminitis (4.8%), and pneumonitis (3.4%). When combined with LCT, OSI primarily resulted in grade 3 AEs like hyponatremia (6.8%), diarrhea (3.4%), empyema (3.4%), and a reduced rate of pneumonitis (1.7%). Of 42 individuals who underwent radiation therapy (RT), 2% experienced a grade 3 AE, potentially linked to the RT, manifesting as non-cardiac chest discomfort. Of the 24 who had surgery, 13% faced surgery-associated grade 3 AEs, which included one arterial injury and two cases of empyema. Frequent mild to moderate AEs (grades 1-2) in the OSI and LCT combination included fatigue (56%), diarrhea (45%), shortness of breath (31%), cough (29%), pneumonitis (10%), difficulty swallowing (12%), and inflammation of the esophagus (7%).
The combination of OSI and LCT is generally safe for pts with EGFR-mutated metastatic NSCLC, and it doesn’t significantly elevate the risk of severe AEs when compared to using OSI on its own.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03410043
Ghandi, S.J., Antonoff, M.B., Blumenschein Jr., G., Liao, Z., Gomez, D.R., Chang, J.Y., Lin, S.H., Cascone, T., Gay, C., Tu, J., Le, X., Tsao, A., O’Reilly, M.S., Ning, M.S., Blakley, C., Rusthoven, C.G., Vaporciyan, A.A., Swisher, S.G., Heymach, J.V., Elamin, Y.Y. 2O – Phase II randomized study of osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR mutant non-small cell lung cancer (NSCLC): Analysis of adverse events (AEs). Journal of Thoracic Oncology (2023) 18 (4S): S35-S88.
