A case of CD74-ROS1-positive lung adenocarcinoma diagnosed by next-generation sequencing achieved long-term survival with pemetrexed regimens

Sep 24, 2026

Previously limited treatment options for advanced non-small cell lung cancer (NSCLC) have been transformed by molecularly targeted therapies and immune checkpoint inhibitors, while next-generation sequencing (NGS) clarifies genomic alterations for drug development. This report describes a 54-year-old woman with left lower lung adenocarcinoma staged T2aN3M1a 11 years earlier. After progression on seventh-line chemotherapy, NGS identified CD74-ROS1 fusion, enabling entrectinib for over 20 months. Long-term survival was achieved, particularly with pemetrexed (PEM) regimens beyond 5 years, highlighting the value of ROS1 testing in responders.

LanguageEnglish

CategoryHealthcare

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Abstract

Background and rationale

Patient history and treatment course

NGS findings and targeted therapy

Outcomes and clinical implications

DOI: 10.1111/1759-7714.15041 CASE REPOR T A case of CD74-ROS1-positive lung adenocarcinoma diagnosed by next-generation sequencing achieved long-term survival with pemetrexed regimens Satoshi Tanaka | Nobuaki Yoshimura | Ryo Asakawa | Satoshi Tobita | Moto Yaga | Kiyonobu Ueno Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan Correspondence Satoshi Tanaka, Department of Respiratory Medicine, Osaka General Medical Center, 3-1-56 Bandai-higashi, Sumiyoshi, Osaka 558-8558, Japan. Email: [satoshi112427@yahoo.co.jp](satoshi112427@yahoo.co.jp) Abstract Previously, cytotoxic drugs were the only option for patients with non-small cell lung cancer (NSCLC) and the prognosis was poor. However, molecularly targeted therapies and immune checkpoint inhibitors represent a breakthrough in the treatment of advanced NSCLC and have improved survival rates. In addition, advances in nextgeneration sequencing (NGS) have revealed the landscape of genomic alterations inpatients with different cancers, aiding in the development of new molecularly targeted drugs. The patient reported here was a 54-year-old woman with left lower lung adenocarcinoma. The lung cancer was staged as T2aN3M1a stageIVA 11 years ago. She had received seven regimens of chemotherapy for 11 years. Among these, pemetrexed (PEM) regimens particularly showed long-term effects totaling more than 5 years. We performed NGS after disease progression of the seventh treatment. NGS revealed CD74-ROS1 fusion and she was treated with entrectinib. She has been taking entrectinib for over 20 months now. Herein, we report a rare case of CD74-ROS1-positive lung adenocarcinoma diagnosed by NGS that achieved long-term survival with cytotoxic drugs, especially PEM regimens. In patients showing favorable clinical response to PEM regimens, physicians should consider testing for ROS1/ALK rearrangement. KEYW ORD S long-term survival, lung adenocarcinoma, next-generation sequencing, pemetrexed, ROS1 rearrangement INTRODUCTION Lung cancer is the leading cause of mortality worldwide. The 1-year survival rate after cytotoxic chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) is 29%, 1 and long-term (>10 years) survival is very rare. Lung cancer treatment has changed drastically in recent years owing to the advent of molecularly targeted therapies and immune checkpoint inhibitors (ICIs), and the survival rate of patients with lung cancer has significantly improved. Driver mutations are detected in more than 60% of NSCLC patients,2 and ROS proto-oncogene 1 (ROS1) rearrangements are found in 1%–2% of patients with NSCLC. Furthermore, next-generation sequencing (NGS) is now acknowledged worldwide, and new molecularly targeted drugs have been developed. Although, only 10%–20% of patients currently benefit from NGS,3 clinical benefit is expected to improve in the future. Herein, we report a case of CD74-ROS1-positive lung adenocarcinoma who achieved long-term (>10 years) survival following cytotoxic drugs (especially PEM regimens) and ICIs and clinically benefited from NGS. CASE REPORT A 54-year-old woman with left anterior chest pain had been diagnosed with left lower lung adenocarcinoma 11 years ago. She had a medical history of schizophrenia and 30 pack-years of smoking history. The lung cancer was This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. staged as T2aN3M1a (PUL) stageIVA. During the course of treatment, EGFR mutation was measured and was negative (cobas EGFR mutation test) . She had received seven regimens of chemotherapy including cytotoxic drugs and ICI for 11 years (Figures 1 and 2) . Among these, pemetrexed (PEM) regimens (cisplatine+PEM and PEM

FAQs

What molecular alteration was identified in this case study?

Next-generation sequencing revealed a CD74-ROS1 fusion in the patient’s tumor tissue.

How long did the patient receive pemetrexed (PEM) regimens and what benefit was observed?

Pemetrexed-containing regimens showed long-term effects totaling more than 5 years, supporting a favorable long-term response.

When was NGS performed and how did it affect treatment selection?

NGS was performed after disease progression following the seventh treatment line; the result guided the use of entrectinib.

Sep 24, 2026

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