Sequential targeted therapy in synchronous dual-primary lung adenocarcinomas with EGFR and RET alterations: a 5-year follow-up case report

TL;DR

A 71-year-old woman with two distinct lung cancers, each with different genetic mutations, was successfully treated with targeted therapies over five years.

Contribution

This case highlights the value of comprehensive molecular testing and sequential targeted therapies in dual-primary lung cancers.

Findings

The patient had two primary lung adenocarcinomas with distinct EGFR and RET genetic alterations.

Sequential treatment with EGFR-TKI, chemotherapy, and pralsetinib led to a sustained response for over three years.

Combination therapy with pralsetinib and anlotinib after resistance achieved a partial response.

Abstract

With the increasing detection of multiple primary pulmonary nodules, accurately distinguishing between multiple primary lung cancers and intrapulmonary metastasis is crucial for diagnosis and treatment. We herein report a case of a 71-year-old female with bilateral multiple primary lung adenocarcinomas, in which separate lesions harbored an EGFR 19del mutation and a RET fusion gene, demonstrating intratumoral genetic heterogeneity. The patient was successively treated with an EGFR-TKI, chemotherapy, and the RET inhibitor pralsetinib, the latter of which maintained a response for over three years. Following the development of resistance, combination therapy with pralsetinib and anlotinib successfully achieved a partial response again. This case underscores the importance of comprehensive molecular testing across multiple lesions to guide precision therapy and provides clinical insights into RET fusion-positive lung cancer treatment and post-resistance combination strategies.

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