ERBB3 amplification

Osimertinib, a third-generation tyrosine kinase inhibitor, is approved as first-line therapy for advanced NSCLC and in the adjuvant setting for Stage IB-IIIA resected NSCLC...Trastuzumab deruxtecan has received accelerated FDA approval in HER2-mutated NSCLC. ADCs offer a possible solution to finding a new treatment that could bypass the intracellular resistance mechanism. In this review article, we summarize the mechanism of ADCs and investigational ADCs for EGFR-mutated NSCLC, which include targets to MET amplification, HER3, Trop2, and EGFR, along with other ADC targets being investigated in NSCLC, and discuss future directions that may arise with ADCs in EGFR-mutated NSCLC.

Alternating therapy with osimertinib and afatinib for treatment-naïve patients with EGFR-mutated advanced NSCLC demonstrated encouraging efficacy. The advantages of this therapy are prevention of acquired resistance via secondary EGFR mutations, including T790M and C797S, and a broadened efficacy against various compound EGFR mutations.

She was then treated with vismodegib for 11 months, first combined with temozolomide and then with bevacizumab, until disease progression was noted on MRI, with no significant toxicities associated with the combination therapy. The current study presents the first documentation in the literature of a primary (non-radiation induced) glioblastoma secondary to Gorlin syndrome. Based on this clinical experience, vismodegib should be considered in combination with standard-of-care therapies for patients with known Gorlin syndrome-associated glioblastomas and sonic hedgehog pathway mutations.

The induction treatment of MIT achieved excellent responses in newly diagnosed PCNSL patients with mild hematologic toxicity. The clearance of ctDNA in CSF/plasma samples was observed during dynamic disease monitoring which was in accord with imageology-based response evaluation.

P+T demonstrated evidence of anti-tumor activity in heavily pre-treated UC pts with ERBB2 amplification or certain mutations . Additional study is warranted to confirm the efficacy of P+T in this pt population.