Early dose reduction of osimertinib in advanced EGFR -mutated non-small cell lung cancer.

Osimertinib has become the standard of care for epidermal growth factor receptor ( EGFR )-mutated non-small cell lung cancer (NSCLC). In order to prevent or treat toxicity, the osimertinib dose may be reduced. However, data regarding the impact of dose reduction during treatment are limited. We aimed to compare the efficacy of osimertinib early dose reduction during the first 3 months of treatment with late dose reduction in EGFR -mutated advanced NSCLC. This retrospective study included patients with EGFR -mutated advanced NSCLC who received osimertinib. We constituted two groups: 'early dose reduction' (early) with patients receiving a reduced dose of osimertinib from 80 to 40 mg within the 3 months of osimertinib initiation and 'late dose reduction' (late) with patients receiving a reduced dose after 3 months of full-dose treatment. Thirty-five patients were included, with 17 and 18 patients in the early and late groups, respectively, and a higher median age in the early group (76 vs. 67 years). The real-world progression-free survival (rwPFS) at 1 year was 70.5% in the early group and 88.9% in the late group ( P  = 0.31). Median rwPFS was 32.7 and 24.6 months ( P  = 0.98), and the median overall survival was 46.9 versus not reached in early and late groups, respectively ( P  = 0.17). Central nervous system rwPFS was not different between the early and late groups: 29.8 and 35.8 months, respectively ( P  = 0.39). We showed that a reduced dose of osimertinib within the first 3 months of treatment, compared to a later reduced dose, could influence treatment response or patient survival.

A Case Series of Multiple Primary Malignancies Among Patients With Advanced Melanoma.

Multiple primary malignancies (MPM) are described as two or more primary tumors within the same individual. The impact of MPM on the tumor microenvironment among patients with melanoma is poorly understood. Here, we describe this unique group of patients who have both advanced melanoma and at least one other primary malignancy and report their survival outcomes. In this study, patients with advanced melanoma and a second primary malignancy were identified. Medical records were reviewed for cancer treatment history. Kaplan-Meier methods were used to derive survival curves and estimate overall survival (OS), and log-rank tests were used to compare OS. Among 11 MPM patients, the most common non-melanoma cancers were breast (n = 3) and thyroid (n = 3). Median OS was 153.5 months for all patients. Median OS for synchronous MPM (sMPM) and metachronous MPM (mMPM) were 83.1 and 196.7 months, respectively (p= 0.10). Median OS was not reached when melanoma was diagnosed first, and 153.5 months when diagnosed second (p= 0.45). For six patients receiving immunotherapy for melanoma, there was a 100% complete response rate. In conclusion, patients with melanoma are at risk of secondary malignancies, including breast and thyroid cancer. The timing of secondary malignancies may impact prognosis. Further study of the impact of immunotherapy on MPM is warranted.