The updated analysis of the phase 3 PHILA trial confirmed the superiority of pyrotinib in combination with trastuzumab and docetaxel over placebo in combination with trastuzumab and docetaxel in sustaining longer progression-free survival and improving overall survival for initial treatment of HER2 positive metastatic breast cancer. The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up. This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population.

These results identify befotertinib as a functional inhibitor of ABCB1 with the capacity to reverse MDR. The findings support its potential as a repurposed agent for combination therapy in tumors with high ABCB1 expression, offering a practical strategy to enhance chemotherapy efficacy.

Notably, compound 3d exhibited in vivo antitumor activity while demonstrating minimal toxicity to normal tissues. These findings collectively suggest that 3d represents a promising candidate for further development as a potential therapeutic agent for hepatocellular carcinoma treatment.

The management of human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) remains a significant clinical challenge, with limited effective and accessible treatment options beyond antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd)...Following chemotherapy and sintilimab failure in August 2025 due to progressive disease, furmonertinib rechallenge at 160 mg/day again induced a response within 5 days, with no grade ≥3 adverse events...The structural homology between HER2 p.Y772_A775dup and EGFR exon 20 "near-loop" insertions may facilitate TKI binding. Furmonertinib emerges as a potential, cost-effective oral therapeutic alternative for this patient population, especially when standard therapies are not feasible, warranting further prospective investigation.

This case suggests that, in EGFR-mutant advanced NSCLC with extensive CNS progression after multiline treatment failure in whom radiotherapy is not feasible, high-dose furmonertinib may represent a potential salvage option and may help inform individualized treatment strategies in this high-risk population. This single case is hypothesis-generating and larger cohorts/prospective studies are needed to confirm efficacy, safety, and appropriate patient selection.

The SACHI trial demonstrated that savolitinib plus osimertinib nearly doubled progression-free survival (PFS) compared with chemotherapy (9.8 vs. 5.4 months; hazard ratio 0.34) in patients with EGFR-mutated, MET-amplified non-small-cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) failure-the first phase 3 evidence for dual EGFR/MET inhibition in this setting.1.

Patients with previously treated EGFR-mutated advanced NSCLC have significant symptom burden and emotional impacts of the disease. These patients would realistically expect a treatment that could improve their quality of life and delay the progression of their disease.

P1/2, N=60, Recruiting, Janssen Research & Development, LLC | Trial completion date: Nov 2028 --> Apr 2029

In the past few years, targeted therapeutic modalities such as antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (the first agent to be granted FDA approval for HER2-mutant NSCLC), alongside selective tyrosine kinase inhibitors (TKIs), including zongertinib and sevabertinib, have demonstrated robust systemic efficacy and notable intracranial penetration. This comprehensive review delineates the molecular landscape and clinical phenotypes of HER2-altered NSCLC, synthesizes interim and mature data from ongoing clinical trials evaluating anti-HER2 therapies, and critically examines efficacy and safety results from different classes of targeted agents. Further research is crucial to uncover potential mechanisms of resistance in NSCLC with HER2 mutations and define sequencing or combinatorial strategies pertinent to optimizing individualized patient management.

P1/2, N=71, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jan 2026 --> Jan 2027

RIPK1-98 modulates cyclin-dependent kinase 2 (CDK2)-dependent cell-cycle regulation, thereby facilitating tumor proliferation in cellular and animal models. Together, these findings suggest that RIPK1-98 serves as a biomarker for cell-cycle progression in LUAD and highlight its potential as a therapeutic target to counteract resistance to first-line treatments, such as osimertinib.

In this real-world study, prior to the approval of osimertinib as adjuvant treatment for resected NSCLC, only one-third of patients received adjuvant treatment within 26 weeks post-surgery, highlighting its underutilization and emphasizing the critical need for early EGFR mutation testing to inform optimal treatment choices.