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Rechallenge With Osimertinib Plus Entrectinib in Lung Cancer With NTRK Fusion: Case Report

By: Kayci Reyer
Posted: Friday, November 18, 2022

A case study presented in Respirology Case Reports describes a patient with EGFR-mutated non–small cell lung cancer (NSCLC) who benefited from the combination of the kinase inhibitor osimertinib plus the TRK inhbitor entrectinib after acquired resistance to osimertinib. The combination therapy was selected because the patient harbored LMNA::NTRK1 fusion in addition to EGFR T790M.

“Identification of resistance mechanisms using serial next-generation sequencing on tumor biopsies or [cell-free DNA] is crucial for the management of EGFR-mutated NSCLC,” concluded Luo et al, of the Zhejiang School of Medicine, Hangzhou, China, and colleagues.

The case report featured a 50-year-old man who had been diagnosed with stage IIIA adenocarcinoma of the right lung and had undergone a lobectomy. Tumor sample testing indicated an EGFR exon 19 deletion accompanied by T790M mutation. After undergoing pemetrexed plus cisplatin treatment followed by recurrent metastatic lung adenocarcinoma, then gefitinib treatment followed by recurrent pleural effusion, the patient received osimertinib. This treatment led to 11 months of progression-free survival. Upon experiencing progressive disease plus increasing pleural effusion, the patient’s treatment was changed to the combination of cisplatin, pemetrexed, and bevacizumab and then to anlotinib plus docetaxel after further disease progression.

The patient experienced disease recurrence 5 months after third-line treatment. At that time, next-generation sequencing revealed an LMNA::NTRK1 fusion. The authors suggest this fusion may be responsible for the patient’s resistance to osimertinib. Rechallenge with osimertinib was then initiated in combination with entrectinib. Although disease progression slowed over the subsequent 5 months, the patient declined to receive further treatment and died 1 month later.

“The outcomes of individual therapies depend on the dominant form of the resistance mechanism, and the effects of combinatorial inhibition of NTRK fusion and the driver EGFR mutation remain to be confirmed by the accumulation of additional case series and further research,” noted the authors.

Disclosure: The study authors reported no conflicts of interest.

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