Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations

Chen, Yen-Fu; Hsieh, Min‐Shu; Wu, Shang‐Gin; Chang, Yih‐Leong; Yu, Chong‐Jen; Yang, James Chih‐Hsin; Yang, Pan‐Chyr; Shih, Jin‐Yuan

doi:10.1016/j.jtho.2016.03.022

Cited by 69 publications

(55 citation statements)

References 48 publications

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“…Chen et al . reported that PEM‐based chemotherapy was effective in NSCLC patients with EGFR mutation, ALK fusion, and ROS 1 rearrangement (overall response rates: 25.5%, 28.1%, and 57.9%, respectively) . Our case also indicated the effectiveness of pemetrexed‐based chemotherapy for NSCLC with a MET exon 14 skipping mutation.…”

Section: Discussionsupporting

confidence: 61%

Efficacy of pembrolizumab for patients with both high PD‐L1 expression and an MET exon 14 skipping mutation: A case report

et al. 2019

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Pembrolizumab has become the standard first‐line treatment for non‐small cell lung cancer (NSCLC) patients with high PD‐L1expression. MET exon 14 skipping is a rare mutation typically found in older, female, and non‐smoking patients with NSCLC. Herein, we report the case of a 71‐year‐old non‐smoking woman who was diagnosed with NSCLC in the left lung. EGFR mutation and ALK fusion were not detected. Because the biopsy specimen showed high PD‐L1 expression with a tumor proportion score of 95%, pembrolizumab was introduced as first‐line therapy, but resulted in no clinical benefit. The patient was subsequently administered chemotherapy with carboplatin and pemetrexed, leading to remarkable tumor shrinkage. A next‐generation sequencing panel analysis revealed a MET exon 14 skipping mutation. Thus, pembrolizumab might not be effective for NSCLC patients with MET exon 14 skipping mutations, even if PD‐L1 expression is high.

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Section: Discussionsupporting

confidence: 61%

Efficacy of pembrolizumab for patients with both high PD‐L1 expression and an MET exon 14 skipping mutation: A case report

et al. 2019

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“…We found that the PFS of patients who treated with pemetrexed-based chemotherapy was 179 days, which was shorter than that in a European prior retrospective study (7.2 months) [14], or in a recently published retrospective study (7.5 months) which was carried out in Taiwan [16]. The difference can be triggered by the study population, tumor heterogeneity and previous treatments of patients.…”

Section: Discussionmentioning

confidence: 63%

Efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement

et al. 2016

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BackgroundROS1 rearrangement is a novel molecular subgroup of non-small-cell lung cancer (NSCLC). This study aimed to investigate the efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement.ResultsA total of 2309 patients received ROS1 fusion detection and 51(2.2%) patients had ROS1 rearrangement. There was no significant difference between ROS1 fusion-positive and fusion-negative cohorts in demographic data. For the ROS1 fusion-positive patients, crizotinb-treated group had a higher overall response rate (ORR, 80.0%), disease control rate (DCR, 90.0%) and longer progression-free survival (PFS, 294 days) compared with the rates in pemetrexed-treated group (ORR, 40.8%; DCR, 71.4%; PFS, 179 days) and non-pemetrexed-treated group (ORR, 25.0%; DCR, 47.7%; PFS, 110 days). Besides, ORR, DCR and PFS were similar in three major ROS1 fusion partners. For the first-line treatment, patients received pemetrexed had a significant longer PFS than those received non-pemetrexed chemotherapy (209 vs. 146 days, P = 0.0107). In pemetrexed-treated cohorts, ROS1-positive patients with low TS expression had a statistically significant longer PFS than those with high TS expression (184 vs. 110 days, P = 0.0105).Materials and methodsWe retrospectively identified patients with NSCLC who were screened for ROS1 fusion using multiplex reverse transcription-polymerase chain reaction (RT-PCR) from October 2013 to February 2016. The thymidylate synthase (TS) mRNA levels were tested using quantitative real-time RT-PCR.ConclusionsCrizotinib was also highly active at treating Chinese NSCLC patients with ROS1 rearrangement. TS expression could predict the efficacy of pemetrexed-based therapy in ROS1 fusion-positive patients.

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“…28,38,41 Lung adenocarcinoma with the ROS1 fusion gene has been reported to be highly responsive to crizotinib or pemetrexed. 5,[42][43][44] However, the current study enrolled a small number of patients, and the effectiveness of both drugs was not obvious in these patients.…”

Section: Discussionmentioning

confidence: 80%

Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion

Liu

et al. 2018

Genes Chromosomes & Cancer

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Young lung cancer patients have several distinct characteristics. However, there are limited epidemiological data of genetic abnormalities in this population. We conducted a prospective cohort study to delineate the various oncogenic driver mutations of lung adenocarcinoma in young Asian patients. We consecutively collected malignant pleural effusions (MPEs) from lung adenocarcinoma patients. RNA was extracted from MPEs for mutation analysis by reverse transcription-polymerase chain reaction and direct sequencing. Selected gene mutations for testing included EGFR, HER2, BRAF, KRAS, PIK3CA, JAK2, MEK1, NRAS, and AKT2 mutations, as well as EML4-ALK, ROS1, and RET fusions. We collected MPEs from 142 patients aged ≤50 years and 730 patients aged >50 years. Patients aged ≤50 years (91%) had a higher incidence of driver gene mutations than those aged >50 years (84%; P = .036), especially EML4-ALK (P < .001) and ROS1 (P < .001). Among patients aged ≤50 years, EGFR mutation was the major oncogenic driver mutation. The mutation rates of other genes were 18% EML4-ALK, 6% ROS1, 5% HER2, 1% RET, 1% BRAF, and 1% KRAS. We did not detect PIK3CA, JAK2, MEK1, NRAS, or AKT2 mutations. No difference in gender or smoking history was noted among those with different driver mutations. Patients who had a good performance status or received appropriate targeted therapy had longer overall survival. In conclusion, lung adenocarcinoma in Asian patients aged ≤50 years had a higher gene mutation rate than in those aged >50 years, especially EML4-ALK and ROS1 fusion. Mutation analysis may be helpful in determining targeted therapy for the majority of these patients.

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Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations

Abstract: ROS1 fusion positivity is probably a favorable factor of pemetrexed-based therapy for patients with lung adenocarcinoma.

Cited by 69 publications

References 48 publications

Efficacy of pembrolizumab for patients with both high PD‐L1 expression and an MET exon 14 skipping mutation: A case report

Efficacy of pembrolizumab for patients with both high PD‐L1 expression and an MET exon 14 skipping mutation: A case report

Efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement

Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion

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