Efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with <i>ROS1</i> rearrangement

Zhang, Limin; Jiang, Tao; Zhao, Chao; Li, Wei; Li, Xuefei; Zhao, Sha; Liu, Xiaozhen; Jia, Yijun; Yang, Hui; Ren, Shengxiang; Zhou, Caicun

doi:10.18632/oncotarget.12612

Cited by 48 publications

(36 citation statements)

References 31 publications

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“…5 Similar anti-tumor activity was observed in several retrospective and single-arm studies. 8–11 Of note, the median PFS on crizotinib in these studies was shorter (range 9.1–13.4 months) than that observed in PROFILE 1001, but ORRs across studies were comparable. Based upon this activity, the U.S. Food and Drug Administration expanded crizotinib’s approval to include patients with advanced, ROS1 -positive NSCLC.…”

Section: Introductionmentioning

confidence: 74%

“…Nonetheless, several recent studies have shown a comparable PFS to our series. 8–11 Interestingly, while ROS1 -positive patients had a longer median PFS on crizotinib compared to ALK -positive patients, there was no difference in OS between cohorts. While we cannot exclude the possibility that this was due to unaccounted for differences in patient characteristics, it is also possible that higher rates of next-generation targeted therapy use among ALK -positive patients may have offset the longer PFS on crizotinib among ROS1 -positive patients.…”

Section: Discussionmentioning

confidence: 99%

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Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

Gainor

Tseng

Yoda

et al. 2017

JCO Precision Oncology

213

222

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PURPOSE The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1–2% of non-small cell lung cancer (NSCLC), conferring sensitivity to treatment with the ALK/ROS1/MET inhibitor crizotinib. Currently, insights into patterns of metastatic spread and mechanisms of crizotinib resistance among ROS1-positive patients are limited. PATIENTS AND METHODS We reviewed clinical and radiographic imaging data of patients with ROS1- and ALK-positive NSCLC in order to compare patterns of metastatic spread at initial metastatic diagnosis. To determine molecular mechanisms of crizotinib resistance, we also analyzed repeat biopsies from a cohort of ROS1-positive patients progressing on crizotinib. RESULTS We identified 39 and 196 patients with advanced ROS1- and ALK-positive NSCLC, respectively. ROS1-positive patients had significantly lower rates of extrathoracic metastases (ROS1 59.0%, ALK 83.2%, P=0.002), including lower rates of brain metastases (ROS1 19.4%, ALK 39.1%; P = 0.033), at initial metastatic diagnosis. Despite similar overall survival between ALK- and ROS1-positive patients treated with crizotinib (median 3.0 versus 2.5 years, respectively; P=0.786), ROS1-positive patients also had a significantly lower cumulative incidence of brain metastases (34% vs. 73% at 5 years; P<0.0001). Additionally, we identified 16 patients who underwent a total of 17 repeat biopsies following progression on crizotinib. ROS1 resistance mutations were identified in 53% of specimens, including 9/14 (64%) non-brain metastasis specimens. ROS1 mutations included: G2032R (41%), D2033N (6%), and S1986F (6%). CONCLUSIONS Compared to ALK rearrangements, ROS1 rearrangements are associated with lower rates of extrathoracic metastases, including fewer brain metastases, at initial metastatic diagnosis. ROS1 resistance mutations, particularly G2032R, appear to be the predominant mechanism of resistance to crizotinib, underscoring the need to develop novel ROS1 inhibitors with activity against these resistant mutants.

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Section: Introductionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

Gainor

Tseng

Yoda

et al. 2017

JCO Precision Oncology

213

222

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“…ROS is a kinase receptor in the insulin receptor superfamily. Rearrangement occurs in 1–2% of non-squamous NSCLC ( 115 , 116 ). ROS-1 chromosomal rearrangement leads to STAT3, PI3K/AKT/mTOR, and RAS/RAF/MAPK activation, followed by cell growth, proliferation, and survival ( 117 ).…”

Section: Ros-1 Chromosomal Translocationmentioning

confidence: 99%

“…ROS-1 chromosomal rearrangement leads to STAT3, PI3K/AKT/mTOR, and RAS/RAF/MAPK activation, followed by cell growth, proliferation, and survival ( 117 ). ROS-1 translocation NSCLC patient is described to be young, female, non-smoker, and with advanced stage adenocarcinoma ( 115 , 117 – 120 ). The 5′ partners and the breakpoints of the ROS1 gene are variable ( 115 , 116 ), which may impact on the biology and benefit to therapy.…”

Section: Ros-1 Chromosomal Translocationmentioning

confidence: 99%

Targeting Novel but Less Common Driver Mutations and Chromosomal Translocations in Advanced Non-Small Cell Lung Cancer

Daoud

Chu

2017

Front. Oncol.

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Discovery of the epidermal growth factor receptor gene mutation and the anaplastic lymphoma kinase chromosomal translocation in non-small cell lung cancer has prompted efforts around the world to identify many less common targetable oncogenic drivers. Such concerted efforts have been variably successful in both non-squamous and squamous cell carcinomas of the lung. Some of the targeted therapies for these oncogenic drivers have received regulatory approval for clinical use, while others have modest clinical benefit. In this mini-review, several of these targets will be reviewed.

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“…The EML4-ALK, CD74-ROS1 and KIF5C-RET constitute the major subset of those fusion variations. [12][13][14] ALK, ROS1 and RET rearrangement positive patients appears to be more common in young and never or light smokers diagnosed with adenocarcinoma. [15] Patients with ALK and ROS1 rearrangements can bene t from TKIs, such as crizotinib, which are now widely used in clinical practice.…”

Section: Introductionmentioning

confidence: 95%

Pathological Signature and Therapeutic Status of NSCLC Patients with Common or Rare Driver Gene Alterations in North China：A real world retrospective study

Zhang

Yang

et al. 2020

Preprint

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Background: Although guidelines recommended to test EGFR/ALK/ROS-1 gene alterations in advanced non-small cell lung cancer (NSCLC) patients before treatment, there is now growing evidence that rare driver genes and mutations also can inform targeted therapy and improve outcomes for this traditionally underrepresented population. This study aimed to describe mutational patterns and linked clinical parameters in a Chinese population-based NSCLC cohort.Methods: This study included patients with pathologically confirmed NSCLC, who were routinely screened for EGFR, KRAS, BRAF, ALK, ROS1, RET, MET, HER2, and PIK3CA mutations by the NMPA approved multi-gene detection kit. The demographic and clinicopathological data, treatment information, clinical outcomes after first-line treatment, as well as nine driver gene mutation statuses and PD-L1 expression level of these patients were retrospectively collected.Results: Finally, 431 patients were enrolled, most patients were male (55.9%), with adenocarcinoma or adenosquamous carcinoma (80.7%) and in stage IV (50.6%). Among all the 431 patients, 61.5% patients were identified with gene mutation including 101 with rare mutation, 164 with 19del or with L858R mutation. Adenocarcinoma patients have a higher mutation rate (73.6%), and the mutations mainly occur in EGFR, KRAS, ALK and HER2. While, the gene mutation characteristics in squamous cell carcinoma patients with were relatively simple, only 2 patients with EGFR 19del and 2 patients with PIK3CA mutation. More PD-L1 expression could detected in patients with rare mutation. The median PFS1 of patients with common mutation (13 months, 95% CI: 9.9-16) was longer than the patients with rare mutation (5 months, 95 % CI: 0-10.5). Conclusions: The clinicopathologic features and clinical treatment status among NSCLC patients with common or rare driver gene mutations were different. The survival of patients with rare mutation was worse than that of patients with common mutation. Therefore, more attention should be paid to the treatment strategy and survival status of patients with rare mutations in clinical practice.

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

Cited by 48 publications

References 31 publications

Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

Targeting Novel but Less Common Driver Mutations and Chromosomal Translocations in Advanced Non-Small Cell Lung Cancer

Pathological Signature and Therapeutic Status of NSCLC Patients with Common or Rare Driver Gene Alterations in North China：A real world retrospective study

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