Minireviews Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 24, 2022; 13(4): 276-286
Published online Apr 24, 2022. doi: 10.5306/wjco.v13.i4.276
New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2
Maria Eugenia Olmedo, Raquel Cervera, Luis Cabezon-Gutierrez, Yolanda Lage, Elena Corral de la Fuente, Ana Gómez Rueda, Xabier Mielgo-Rubio, Juan Carlos Trujillo, Felipe Couñago
Maria Eugenia Olmedo, Yolanda Lage, Ana Gómez Rueda, Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid 28034, Spain
Raquel Cervera, Department of Medical Oncology, Del Henares University Hospital, Coslada 28822, Madrid, Spain
Luis Cabezon-Gutierrez, Medical Oncology, Hospital Universitario de Torrejón, Torrejón de Ardoz 28850, Madrid, Spain
Elena Corral de la Fuente, Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid 28034, Spain
Xabier Mielgo-Rubio, Department of Medical Oncology, Foundation Alcorcón University Hospital, Alcorcón 28922, Madrid, Spain
Juan Carlos Trujillo, Department Thoracic Surgery, Hospital de la Santa Creu I Sant Pau, Barcelona 08029, Catalonia, Spain
Juan Carlos Trujillo, Department of Surgery, Universitat Autonoma de Barcelona, Barcelona 08029, Catalonia, Spain
Felipe Couñago, Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo 28223, Madrid, Spain
Felipe Couñago, Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
Felipe Couñago, Medicine Department, School of Biomedical Sciences, Universidad Europea de Madrid, Madrid 28670, Spain
ORCID number: Maria Eugenia Olmedo (0000-0002-0643-493X); Raquel Cervera (0000-0001-9870-8768); Luis Cabezon-Gutierrez (0000-0002-3468-3626); Yolanda Lage (0000-0002-9351-3184); Elena Corral de la Fuente (0000-0002-7030-2413); Ana Gómez Rueda (0000-0003-4215-8474); Xabier Mielgo-Rubio (0000-0002-0985-6150); Juan Carlos Trujillo (0000-0002-3370-0860); Felipe Couñago (0000-0001-7233-0234).
Author contributions: Olmedo ME, Cervera R, Cabezón L, Lage Y, Corral de la Fuente E, Gómez Rueda A performed research and wrote the paper; Couñago F, Trujillo JC, Mielgo-Rubio X contributed a critical review of the manuscript for important intellectual content; Mielgo-Rubio X contributed to management of the manuscript and submission.
Conflict-of-interest statement: Xabier Mielgo-Rubio declares the following conflicts of interest: Advisory role; Boehringer-Ingelheim, AstraZeneca, Bristol Myers Squibb. Speakers’ bureau; Roche, AstraZeneca, Bristol Myers Squibb, MSD, Abbott. Research funding; Bristol Myers Squibb. Luis Cabezón-Gutiérrez received speaker or consulting fees from Angelini, Grunenthal, Kyowa Kirin, Mundipharma, Pfizer, Roche, Rovi, Leo Pharma, Merck Serono, Ipsen Pharma, Lilly, Amgen, Boehringer Ingelheim, and AstraZeneca; The remaining authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Maria Eugenia Olmedo, MD, PhD, Consultant Physician-Scientist, Department of Medical Oncology, Ramón y Cajal University Hospital, M-607, km. 9, 100, Madrid 28034, Spain.
Received: April 19, 2021
Peer-review started: April 19, 2021
First decision: July 6, 2021
Revised: September 5, 2021
Accepted: April 3, 2022
Article in press: April 3, 2022
Published online: April 24, 2022


The 2004 discovery of EGFR mutations, followed by ALK rearrangements, ushered in a targeted therapy era for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC. In the last decade, rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies. Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets, including RET, NTRK fusions, c-MET alterations, and activating mutations in KRAS, BRAF, and HER2, all with frequencies greater than 1%. Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development. This review updates the therapeutic arsenal that especially targets those genes.

Key Words: BRAF, NTRK, KRAS, MET, RET, HER2, Non-small cell lung cancer, Targeted therapy, Uncommon mutations

Core Tip: Compared to other types of cancer, non-small cell lung cancer (NSCLC) is highly genetically altered. Outside of EGFR, ALK, and ROS1, reflecting 15%-20% of clinical practice, other molecular alterations with important recent advances in their therapeutic arsenal and already in phase II/III trials are BRAF, KRAS, RET, MET, NTRK, and HER2. The goal is to achieve, compared to conventional treatments such as chemotherapy, better symptom control, better response rates, and improved progression-free survival and overall survival in patients with NSCLC.


Approximately 60% of lung adenocarcinomas harbour molecular alterations in driver oncogenes, with incidence, which varies according to ethnic origin and alteration, as follows: epidermal growth factor receptor (EGFR) mutation, 15%-20%[1]; anaplastic lymphoma kinase (ALK) rearrangement, 5%-7%[2]; and c-ros 1 (ROS1) rearrangement, approximately 1%[3]. There has been an impressive improvement in survival in response to tyrosine kinase inhibitors (TKIs), which also have a better toxicity profile compared to standard chemotherapy.

The consequent improvement in molecular understanding of non-small cell lung carcinoma (NSCLC) has allowed increasingly exhaustive molecular classification as well as identification of a subset of patients susceptible to specifically targeted therapy. The outcome of massive gene-sequencing platforms with higher throughput than gene-to-gene determinations is that patients can be offered more treatments that more specifically impact on their quality of life and survival. The current recommendation is to carry out a comprehensive molecular analysis using multiplex platforms – next-generation sequencing (NGS) – if available, considering advantages in terms of coverage, time, and a favorable economic profile[4]. NGS is capable of detecting less common or difficult-to-identify oncogenes, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (30%-35%), V-raf murine sarcoma viral oncogene homolog B (BRAF) mutations (4%-5%), mesenchymal-epithelial transition factor (c-MET) alterations, exon 14 insertions and/or amplifications (5%-9%), rearrangements during transfection (RET) (1%-2%), human epidermal growth factor receptor 2 (HER2) mutations (2%), and neurotrophic receptor tyrosine kinase (NTRK) fusions (< 1%)[5]. Identifying these alterations is increasingly important, as new specific drugs in clinical development show promise in terms of modifying the natural history of NSCLC. We focus on direct inhibitors of pathways and their practice-changing results.


Present in 2%-3% of NSCLC cases, the BRAF mutation is mostly encountered in patients diagnosed with adenocarcinoma[6]. The most common variant is V600E, found in 50%-60% of patients with BRAF-mutated (BRAFm) NSCLC. Not clear is the prognostic value of BRAF-V600E compared with non-V600E or with the rest of patients with NSCLC[7].

The drugs used to date for this molecular alteration are the same TKIs that have proven to be effective in treating melanoma, a tumour with high BRAFm frequency.

Table 1 summarizes the efficacy of the main drugs used to date. The best results have been reported for dabrafenib combined with trametinib, which attempt to block the MAPK pathway at two different sites (BRAF and MEK), thus overcoming possible tumour resistance to TKIs. The BRF113928 study in patients who received 2-4 Lines of therapy reported an objective response rate (ORR) of 63.2%, and a first-line ORR of 64%[8-12].

Table 1 Phase II trials with BRAF inhibitors.
ORR (%)
PFS (mo)
OS (mo)
Vemurafenib BRAF V600E[8]6237.16.5115.38
Vemurafenib V600E[9]10105.210
Vemurafenib non-V600E[9]1744.9NRNR
Dabrafenib in 2nd line or beyond[10]7833.35.512.7
Dabrafenib + trametinib in 2nd line or beyond[11]5763.210.218.2
Dabrafenib + trametinib en 1st line[12]366410.924.6

However, the absence of comparative data for first and subsequent lines of therapy as currently used for this group of patients means that it is not possible to confirm significant clinical benefit and efficacy over alternative therapies. Dabrafenib and trametinib may therefore be of use for patients for whom standard therapies are not possible or have failed.

Phase II studies are also currently recruiting for the encorafenib + binimetinib (NCT04526782) and cobimetinib + vemurafenib (NCT03178552) combinations.


KRAS is the most common mutation in NSCLC, present in up to 30% of adenocarcinomas[13]. In 80% of cases it is located at codon 12, and the most frequent mutation is KRAS-G12C, reflected in 13% of all lung adenocarcinomas. It is considered practically exclusive in relation to any other clinical practice drivers, although co-occurrences have been found with alterations in TP53, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B), STK11, and KEAP1 (Kelch Like ECH Associated Protein 1)[14].

While KRAS has been a therapeutic target for decades, no direct therapeutic option has been established. In recent years, new direct inhibitors of KRAS-G12C have emerged. Phase II trial results for sotorasib, an irreversible and highly selective KRAS-G12C inhibitor, have positioned it as a major lung cancer milestone for the KRAS mutation[15,16]; for 126 included patients, the ORR was 37.1%, there were three complete responses (CRs) and 43 partial responses (PRs), and the disease control rate was 80.6%, for a median progression-free survival (PFS) of 6.8 mo and a good tolerability profile. Based on those data, an application for marketing authorization has been submitted to the FDA and EMA.

In two presentations at the 32nd Symposium on Cancer Therapeutics and Molecular Targets EORTC-NCI-AACR[17,18], investigators from the KRYSTAL-1 phase I and II clinical trial reported that adagrasib clinical activity has been demonstrated in previously treated patients with NSCLC and the KRAS-G12C mutation. Promising preliminary data for this drug are to be further evaluated in trials, along with combinations, including with pembrolizumab in the KRYSTAL-7 phase 2 trial (NCT04613596) of untreated patients[19].


RET gene fusions and activating point mutations are primary oncogenic drivers that are usually mutually exclusive with other oncogenic driver alterations[20]. Among the various oncogene drivers in NSCLC, the RET gene is involved in various chromosomal rearrangements, found in 1%-2% of all NSCLC patients[21].

Most of the drugs active against RET are TKIs. Multikinase inhibitors initially studied in phase II clinical trials include cabozantinib, nintedanib, lenvatinib, vandetanib, and sorafenib, each with a different ORR (Table 2)[22-25].

Table 2 Phase II trials with multikinase RET inhibitors.
Cabozantinib[22]2528%5.5 mo9.9 mo
Vandetanib[23]1818%4.5 mo11.6 mo
Lenvatinib[24]2516%7.3 moNR
Selpercatinib[26]10564% in platinum chemotherapy pretreated90% in response at 6 moNR
85% in platinum chemotherapy naïve
Pralsetinib[27]10661% in platinum chemotherapy pretreatedNRNR
73% in platinum chemotherapy naïve

Selpercatinib (LOXO-292) is a highly selective, potent, central nervous system (CNS)-active, small-molecule RET kinase inhibitor. Selpercatinib has nanomolar potency against wild-type RET and other RET alterations, including the KIF5B-RET fusion and V804M gatekeeper mutation, in both enzyme and cellular assays, with minimal activity against other kinase and non-kinase targets[26].

In the LIBRETTO-001 phase I/II trial, selpercatinib treatment demonstrated clinically meaningful responses and sustained antitumour activity, for a manageable toxicity profile, in both heavily pre-treated and treatment-naive patients, and including patients with brain metastases and with RET fusion-positive NSCLC (intracranial CNS (n = 10/11): ORR 91%). In May 2020, selpercatinib was approved by the FDA under the Accelerated Approval programme for the treatment of RET-altered cancers (NSCLC and thyroid cancer)[27].

Pralsetinib (BLU-667) is a novel small-molecule RET inhibitor, designed for high potency and selectivity against oncogenic RET alterations, including the most frequent RET rearrangements (e.g., KIF5B–RET and CCDC6–RET). The global phase I/II ARROW study has demonstrated broad and durable antitumour activity for pralsetinib in a variety of advanced RET-altered solid tumours, including RET fusion+ NSCLC. For 354 patients with advanced solid tumours who received pralsetinib as first-line treatment, the ORR was 73%, for a 12% CR rate (n = 26). Treatment-related adverse events were most frequently grade 1-2[28]. Table 2 summarizes the activity of the different TKIs against RET.

RXDX-105 differs from the other multi-targeted TKIs because it has RET activity but limited activity against the vascular endothelial growth factor (VEGF) receptors. In RET TKI-naive patients, the drug showed modest activity. Subset analysis revealed that the ORR varied by fusion partner. ORRs were 0% (0/20) in the RET-KIF5B rearrangement subset (the most common rearrangement) and 67% (6/9) in the RET-non-KIF5B rearrangement subset[29].


c-MET is an oncogene that encodes a tyrosine kinase receptor whose ligand is hepatocyte growth factor (HGF). Alterations in c-MET (mutation, amplification, or overexpression) cause abnormal receptor activity that is associated with rapid tumour growth, greater tumour aggressiveness, and resistance to cancer treatments[30].

c-MET amplification is present in 1%-6% of patients with NSCLC. Skipping mutation of exon 14 occurs in 3%-4% of cases, most frequently for non-squamous and sarcomatoid histologies (20%-30%). This alteration occurs most frequently in older patients and in smokers.

Selective and non-selective c-MET inhibitors (Tables 3 and 4) are currently available that can impact on survival in patients with NSCLC. The first drug to demonstrate efficacy with this tumour subtype was crizotinib: In the PROFILE 1001 study, the ORR was 32% and PFS was 7.3 mo[31].

Table 3 Mesenchymal-epithelial transition factor inhibitors.
Other targets
IC50 (nmol/L)
CrizotinibNoIaALK, ROS122.5
CabozantinibNoIIRET, ROS1, VEGFR2, KIT7.8
MerestinibNoIITIE-1, AXL, ROS1, DDR1/2, FLT3, MERTK, RON8.1
GlesatinibNoIIMET, VEGFR, RON, TIE-221.1
Table 4 Clinical trials of mesenchymal-epithelial transition factor inhibitors.
Clinical trial
GlesatinibNCT029549912Glesatinib + NivolumabORRActive, not recruiting
MerestinibNCT029209962MerestinibORRActive, not recruiting
SavolitinibNCT028974792SavolitinibORRActive, not recruiting
Telisotuzumab (ABBV 399)NCT035747532ABBV-399ORRCompleted
JNJ-61186372NCT026097761JNJ-61186372ORR, securityRecruiting
EGFR and MET mab

Capmatinib is another drug that has been shown to be active: in the GEOMETRY MONO-1 study, the ORR was 41% and PFS was 5.4 mo in previously treated patients; in first-line patients, the ORR was 68% and PFS was 12.4 mo, while ORR was 54% for intracranial activity[32]. In the VISION study, tepotinib achieved an ORR greater than 40%, irrespective of the therapy line, PFS of 8.5 mo, and an ORR of 55% for intracranial activity[33]. Regarding MET amplification, TKIs have only significantly benefited tumours with a high level of amplification (MET/CEP7 > 5), for an ORR of 40% with crizotinib and of 47% with capmatinib.

Amplification, which may appear de novo or as a mechanism of resistance to the targeted treatment of EGFR tumours, is present in 4% of cases of progression to first/second generation inhibitors, and in 15% of cases of progression to osimertinib. Being explored, therefore, is the combination of EGFR inhibitors and MET inhibitors.

The TATTON study explored osimertinib combined with savolitinib in patients with NSCLC and mutated EGFR. In the group that received initial treatment with a first/second generation inhibitor, the ORR was 52%, while in the group that received osimertinib, the ORR was 25%, for an acceptable toxicity profile[34].

As for immunotherapy, despite the fact that the tumours may present with elevated PD-L1 expression, the benefit reported for retrospective studies by a French group was limited, at an ORR of 16% and PFS of 3.4 mo[35].


The tropomyosin receptor kinase (TRK) family consists of three tyrosine kinase receptors – TRKA, TRKB, and TRKC isoforms, encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively – that are mainly expressed in the nervous system. Their fusions involve some 80 associated genes and they are known oncogenic drivers[35-38]. The incidence of NTRK fusions in NSCLC is estimated to be 0.1%-0.2%, affecting a population that is unselected in terms of sex, age, or smoking[37].

Currently, two first-generation TKIs targeting NTRK fusions have been approved by the FDA and the EMA: entrectinib (multikinase ALK, ROS1, and pan-TRK inhibitor) and larotrectinib (selective pan-TRK inhibitor). Both have demonstrated great efficacy (irrespective of histology or fusion gene) and intracranial activity, as well as good toxicity profiles[38-41].

Larotrectinib efficacy and safety in patients with solid tumours and NTRK fusions have been evaluated in two registrational phase I/II studies (NCT02122913 and NCT02576431). By July 2020, 20 patients with TRK fusion-positive lung cancer had been treated. Joint analysis of those studies, yielded an ORR of 73% and a CR rate of 7% for patients with lung cancer. The median PFS and OS in lung cancer patients was 35.4 and 40.7 mo. Among patients with baseline central nervous system metastases, the ORR was 63%. Reported adverse events were mostly grade 1-2[38].

Entrectinib was evaluated in the phase I ALKA-372-001 trial, phase I STARTRK-1 trial and phase II STARTRK-2 basket trial. For the 10 patients with NSCLC, the ORR was 70%, the CR rate was 10%, and PFS was 14.9 mo. Entrectinib showed a good toxicity profile; most adverse events were grade 1 or 2 and reversible, e.g., dysgeusia, constipation, fatigue, diarrhoea, oedema, and dizziness[39].

Selitrectinib (LOXO 195), repotrectinib (TPX-0005), and taletrectinib (DS-6051b/AB-106) are second-generation drugs capable of inhibiting on-target resistance of NTRK[37,40]. They are currently being evaluated in phase I/II clinical trials in patients with NTRK-positive tumours who have progressed to first-generation inhibitors (NCT03215511, EudraCT 2017-004246-20, NCT04094610, TRIDENT-1: NCT03093116, NCT02279433).


HER2 is a cell growth promoting protein, a member of the ERBB family of tyrosine kinase receptors expressed on the surface of many types of tumours.

Overexpression, which occurs in 2%-20% of cases depending on the immunohistochemistry (IHC) level (IHC2+/3+), is associated with a poor prognosis. HER2 amplification occurs, especially in adenocarcinomas, in around 3% of cases without prior treatment and in approximately 10% of cases of EGFR resistance to TKIs[42].

HER2 mutations (HER2m) – usually consisting of insertions in exon 20, especially in codon 776 – appear mainly in women, in adenocarcinoma cases, and in the Asian population, and never in smokers. The insertions cause constitutive activation of the receptor, making it sensitive to dual TKI action against EGFR and HER2, but not exclusively to EGFR inhibition[43].

The therapies commonly used to target HER2 in breast cancer have not had the same results for NSCLC. The emergence of new TKIs and conjugated antibodies have given a new boost to therapies for this molecular alteration in NSCLC (Table 5). Reported for the largest retrospective EUHER2 study, which included patients with HER2 exon 20 insertions, was an ORR of 7.4% for treatment with the TKIs afatinib, lapatinib, and neratinib; for the trastuzumab antibody and the trastuzumab emtansine (T-DM1) antibody-drug conjugate, the ORR was a more effective 50.9%, but that treatment was in most cases combined with chemotherapy[44,45].

Table 5 Phase II trials with HER2 inhibitors.
Molecular alteration
PFS (mo)
OS (mo)
Dacomitinib[44]HER2 mutant2612NRNR
Neratinib + Trastuzumab[46]HER2 mutant5217410.2
Neratinib + Temsirolimus[46]HER2 mutant4319415.1
Pyrotinib[47]HER2 mutant60306.914.4
Poziotinib[48]HER2 mutant90285.5NR
Trastuzumab emtansine[49]IHC 2+2902.612.2
IHC 3+20202.715.3
Trastuzumab deruxtecan[49]HER-2 mutant4261.9NRNR
Trastuzumab deruxtecan[49]IHC 2+3925.65.411.3
IHC 3+1020

Two phase II studies, of neratinib combined with trastuzumab in HER2m patients in first or successive therapy lines (NCT01953926) and of neratinib with temsirolimus (NCT01827267), have reported ORRs of 17% and 19%, respectively[46]. Zhou et al[47] explored the efficacy of pyrotinib in monotherapy, reporting an ORR of 30%, median PFS of 6.9 mo, and overall survival (OS) of 14.4 mo; the main toxicity, as with other HER2-targeting TKIs such as neratinib and lapatinib, was diarrhoea. In the phase II ZENITH20 trial of poziotinib, another pan-HER TKI, for the HER2m treatment the ORR was 28%, PFS was 5.5 mo, and the toxicity profile was similar to that for pyrotinib[48].

In addition to the HER2 TKIs, also being evaluated in this setting are antibody-drug conjugates such as T-DM1 and trastuzumab deruxtecan (DS-8201, T-Dxd). Peters et al[49]. explored responses to TDM-1 in 49 patients with IHC2+/3+ overexpression, reporting no response for the IHC2+ cohort and 4 PRs for the IHC3+ cohort (20%). Better data is available for trastuzumab deruxtecan. For 42 patients with HER2m in the DESTINY-Lung01 cohort, the ORR was 62%, PFS was 14 mo; median OS was not achieved, while OS was 24.5% in the IHC2+/3+ overexpression cohorts[50].

To confirm the PFS benefit, a phase III trial of pyrotinib vs docetaxel called PYRAMID-1 (NCT04447118) is ongoing.


Compared to traditional chemotherapy, the improved TKI targeting of EGFR mutations and ALK/ROS1 translocations has led to significant efficacy and quality of life improvements in the management of patients with NSCLC. While this subgroup of patients inevitably develops resistance to TKIs, this can be overcome by developing new next-generation TKIs or drugs aimed at overcoming resistance from the outset or from the time of discovery[51,52].

These developments may also be transferable to the treatment of patients with other molecular alterations of BRAF, KRAS, RET, MET, NTRK and HER2. As can be seen above, a growing number of drugs and combinations are becoming available that target these alterations, often producing a significant improvement in response and survival rates.

Given the many common and rare molecular alterations in NSCLC, full-panel multigene NGS is recommended rather than gene-by-gene sequencing, as not only is it more cost-effective, it allows patients with a target to be easily identified and treated, whether with an approved drug or in a clinical trial of a promising drug[53-55].


Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Oncology

Country/Territory of origin: Spain

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Zheng G, United States S-Editor: Gong ZM L-Editor: A P-Editor: Gong ZM

1.  Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020;31:1536-1544.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 64]  [Cited by in F6Publishing: 56]  [Article Influence: 32.0]  [Reference Citation Analysis (0)]
2.  Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385-2394.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2466]  [Cited by in F6Publishing: 2756]  [Article Influence: 274.0]  [Reference Citation Analysis (0)]
3.  Kalemkerian GP, Narula N, Kennedy EB, Biermann WA, Donington J, Leighl NB, Lew M, Pantelas J, Ramalingam SS, Reck M, Saqi A, Simoff M, Singh N, Sundaram B. Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018;36:911-919.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 263]  [Cited by in F6Publishing: 296]  [Article Influence: 65.8]  [Reference Citation Analysis (0)]
4.  Shaw AT, Riely GJ, Bang YJ, Kim DW, Camidge DR, Solomon BJ, Varella-Garcia M, Iafrate AJ, Shapiro GI, Usari T, Wang SC, Wilner KD, Clark JW, Ou SI. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019;30:1121-1126.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 200]  [Cited by in F6Publishing: 224]  [Article Influence: 100.0]  [Reference Citation Analysis (0)]
5.  Ekman S. How selecting best therapy for metastatic NTRK fusion-positive non-small cell lung cancer? Transl Lung Cancer Res. 2020;9:2535-2544.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Chen D, Zhang LQ, Huang JF, Liu K, Chuai ZR, Yang Z, Wang YX, Shi DC, Liu Q, Huang Q, Fu WL. BRAF mutations in patients with non-small cell lung cancer: a systematic review and meta-analysis. PLoS One. 2014;9:e101354.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 59]  [Cited by in F6Publishing: 68]  [Article Influence: 7.4]  [Reference Citation Analysis (0)]
7.  Couraud S, Barlesi F, Fontaine-Deraluelle C, Debieuvre D, Merlio JP, Moreau L, Beau-Faller M, Veillon R, Mosser J, Al Freijat F, Bringuier PP, Léna H, Ouafik L, Westeel V, Morel A, Audigier-Valette C, Missy P, Langlais A, Morin F, Souquet PJ, Planchard D; Biomarkers France Contributors. Clinical outcomes of non-small-cell lung cancer patients with BRAF mutations: results from the French Cooperative Thoracic Intergroup biomarkers France study. Eur J Cancer. 2019;116:86-97.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 11]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
8.  Subbiah V, Gervais R, Riely G, Hollebecque A, Blay JY, Felip E, Schuler M, Gonçalves A, Italiano A, Keedy V, Chau I, Puzanov I, Raje NS, Meric-Bernstam F, Makrutzki M, Riehl T, Pitcher B, Baselga J, Hyman DM. Efficacy of Vemurafenib in Patients With Non-Small-Cell Lung Cancer With BRAF V600 Mutation: An Open-Label, Single-Arm Cohort of the Histology-Independent VE-BASKET Study. JCO Precis Oncol. 2019;3:1-9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 20]  [Article Influence: 5.7]  [Reference Citation Analysis (0)]
9.  Mazieres J, Cropet C, Montané L, Barlesi F, Souquet PJ, Quantin X, Dubos-Arvis C, Otto J, Favier L, Avrillon V, Cadranel J, Moro-Sibilot D, Monnet I, Westeel V, Le Treut J, Brain E, Trédaniel J, Jaffro M, Collot S, Ferretti GR, Tiffon C, Mahier-Ait Oukhatar C, Blay JY. Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations. Ann Oncol. 2020;31:289-294.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 62]  [Cited by in F6Publishing: 72]  [Article Influence: 31.0]  [Reference Citation Analysis (0)]
10.  Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, Souquet PJ, Smit EF, Groen HJ, Kelly RJ, Cho BC, Socinski MA, Pandite L, Nase C, Ma B, D'Amelio A Jr, Mookerjee B, Curtis CM Jr, Johnson BE. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17:642-650.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 256]  [Cited by in F6Publishing: 294]  [Article Influence: 42.7]  [Reference Citation Analysis (0)]
11.  Planchard D, Besse B, Groen HJM, Souquet PJ, Quoix E, Baik CS, Barlesi F, Kim TM, Mazieres J, Novello S, Rigas JR, Upalawanna A, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984-993.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 500]  [Cited by in F6Publishing: 561]  [Article Influence: 83.3]  [Reference Citation Analysis (0)]
12.  Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland Å, Giannone V, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18:1307-1316.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 485]  [Cited by in F6Publishing: 431]  [Article Influence: 97.0]  [Reference Citation Analysis (0)]
13.  Veluswamy R, Mack PC, Houldsworth J, Elkhouly E, Hirsch FR. KRAS G12C-Mutant Non-Small Cell Lung Cancer: Biology, Developmental Therapeutics, and Molecular Testing. J Mol Diagn. 2021;23:507-520.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 16]  [Article Influence: 13.0]  [Reference Citation Analysis (0)]
14.  Arbour KC, Jordan E, Kim HR, Dienstag J, Yu HA, Sanchez-Vega F, Lito P, Berger M, Solit DB, Hellmann M, Kris MG, Rudin CM, Ni A, Arcila M, Ladanyi M, Riely GJ. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2018;24:334-340.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 198]  [Cited by in F6Publishing: 211]  [Article Influence: 39.6]  [Reference Citation Analysis (0)]
15.  Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020;383:1207-1217.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 598]  [Cited by in F6Publishing: 652]  [Article Influence: 299.0]  [Reference Citation Analysis (0)]
16.  Li BT  CodeBreaK 100: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutated Non-small Cell Lung Cancer. IASLC 2021; Abstract PS01.07.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Jänne PA, Rybkin II, Spira AI, Riely GJ, Papadopoulos KP, Sabari JK, Johnson ML, Heist RS, Bazhenova L, Barve M, Pacheco JM, Leal TA, Velastegui K, Cornelius C, Olson P, Christensen JG, Kheoh T, Chao RC, Ou SHI. KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Advanced/ Metastatic Non–Small-Cell Lung Cancer (NSCLC) Harboring KRAS G12C Mutation. Eur J Cancer. 2020;138:S1-S2.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 73]  [Cited by in F6Publishing: 36]  [Article Influence: 36.5]  [Reference Citation Analysis (0)]
18.  Johnson ML, Ou SHI, Barve M, Rybkin II, Papadopoulos KP, Leal TA, Velastegui Karen, Christensen JG, Kheoh T, Chao RC, Weiss J. KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Patients With Colorectal Cancer (CRC) and Other Solid Tumors Harboring a KRASG12C Mutation. Eur J Cancer. 2020;138:S2.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 20]  [Article Influence: 19.5]  [Reference Citation Analysis (0)]
19.  Mirati Therapeutics Inc  Phase 2 trial of MRTX849 plus pembrolizumab for NSCLC with KRAS C12C mutation KRYSTAL-7. Acailable from:  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Bronte G, Ulivi P, Verlicchi A, Cravero P, Delmonte A, Crinò L. Targeting RET-rearranged non-small-cell lung cancer: future prospects. Lung Cancer (Auckl). 2019;10:27-36.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 23]  [Article Influence: 6.0]  [Reference Citation Analysis (0)]
21.  Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543-550.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3395]  [Cited by in F6Publishing: 3664]  [Article Influence: 424.4]  [Reference Citation Analysis (0)]
22.  Drilon A, Rekhtman N, Arcila M, Wang L, Ni A, Albano M, Van Voorthuysen M, Somwar R, Smith RS, Montecalvo J, Plodkowski A, Ginsberg MS, Riely GJ, Rudin CM, Ladanyi M, Kris MG. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 2016;17:1653-1660.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 270]  [Cited by in F6Publishing: 264]  [Article Influence: 45.0]  [Reference Citation Analysis (0)]
23.  Lee SH, Lee JK, Ahn MJ, Kim DW, Sun JM, Keam B, Kim TM, Heo DS, Ahn JS, Choi YL, Min HS, Jeon YK, Park K. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial. Ann Oncol. 2017;28:292-297.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 125]  [Cited by in F6Publishing: 145]  [Article Influence: 25.0]  [Reference Citation Analysis (0)]
24.  Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer. 2019;138:124-130.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 49]  [Article Influence: 14.3]  [Reference Citation Analysis (0)]
25.  Horiike A, Takeuchi K, Uenami T, Kawano Y, Tanimoto A, Kaburaki K, Tambo Y, Kudo K, Yanagitani N, Ohyanagi F, Motoi N, Ishikawa Y, Horai T, Nishio M. Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer. Lung Cancer. 2016;93:43-46.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 34]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
26.  Subbiah V, Velcheti V, Tuch BB, Ebata K, Busaidy NL, Cabanillas ME, Wirth LJ, Stock S, Smith S, Lauriault V, Corsi-Travali S, Henry D, Burkard M, Hamor R, Bouhana K, Winski S, Wallace RD, Hartley D, Rhodes S, Reddy M, Brandhuber BJ, Andrews S, Rothenberg SM, Drilon A. Selective RET kinase inhibition for patients with RET-altered cancers. Ann Oncol. 2018;29:1869-1876.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 198]  [Cited by in F6Publishing: 216]  [Article Influence: 66.0]  [Reference Citation Analysis (0)]
27.  Drilon A, Oxnard GR, Tan DSW, Loong HHF, Johnson M, Gainor J, McCoach CE, Gautschi O, Besse B, Cho BC, Peled N, Weiss J, Kim YJ, Ohe Y, Nishio M, Park K, Patel J, Seto T, Sakamoto T, Rosen E, Shah MH, Barlesi F, Cassier PA, Bazhenova L, De Braud F, Garralda E, Velcheti V, Satouchi M, Ohashi K, Pennell NA, Reckamp KL, Dy GK, Wolf J, Solomon B, Falchook G, Ebata K, Nguyen M, Nair B, Zhu EY, Yang L, Huang X, Olek E, Rothenberg SM, Goto K, Subbiah V. Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2020;383:813-824.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 259]  [Cited by in F6Publishing: 282]  [Article Influence: 129.5]  [Reference Citation Analysis (0)]
28.  ainor JF, Curigliano G, Kim DW, Ho Lee D, Besse B, Baik CS, et al Registrational dataset from the phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET fusion+ non-small cell lung cancer (NSCLC).   J Clin Oncol 38: 2020 (suppl; abstr 9515).  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Drilon A, Fu S, Patel MR, Fakih M, Wang D, Olszanski AJ, Morgensztern D, Liu SV, Cho BC, Bazhenova L, Rodriguez CP, Doebele RC, Wozniak A, Reckamp KL, Seery T, Nikolinakos P, Hu Z, Oliver JW, Trone D, McArthur K, Patel R, Multani PS, Ahn MJ. A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105. Cancer Discov. 2019;9: 384-395.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 63]  [Cited by in F6Publishing: 69]  [Article Influence: 15.8]  [Reference Citation Analysis (0)]
30.  Salgia R, Sattler M, Scheele J, Stroh C, Felip E. The promise of selective MET inhibitors in non-small cell lung cancer with MET exon 14 skipping. Cancer Treat Rev. 2020;87: 102022.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 38]  [Article Influence: 18.0]  [Reference Citation Analysis (0)]
31.  Drilon A, Clark JW, Weiss J, Ou SI, Camidge DR, Solomon BJ, Otterson GA, Villaruz LC, Riely GJ, Heist RS, Awad MM, Shapiro GI, Satouchi M, Hida T, Hayashi H, Murphy DA, Wang SC, Li S, Usari T, Wilner KD, Paik PK. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med. 2020;26: 47-51.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 159]  [Cited by in F6Publishing: 171]  [Article Influence: 79.5]  [Reference Citation Analysis (0)]
32.  Wolf J, Seto T, Han JY, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim TM, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS; GEOMETRY mono-1 Investigators. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N Engl J Med. 2020;383:944-957.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 283]  [Cited by in F6Publishing: 310]  [Article Influence: 141.5]  [Reference Citation Analysis (0)]
33.  Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han JY, Kim YC, Chang GC, Tsai CL, Yang JC, Chen YM, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV, Le X. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020;383:931-943.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 259]  [Cited by in F6Publishing: 284]  [Article Influence: 129.5]  [Reference Citation Analysis (0)]
34.  Sequist LV, Han JY, Ahn MJ, Cho BC, Yu H, Kim SW, Yang JC, Lee JS, Su WC, Kowalski D, Orlov S, Cantarini M, Verheijen RB, Mellemgaard A, Ottesen L, Frewer P, Ou X, Oxnard G. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study. Lancet Oncol. 2020;21:373-386.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 170]  [Cited by in F6Publishing: 187]  [Article Influence: 85.0]  [Reference Citation Analysis (0)]
35.  Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, Thai AA, Mascaux C, Couraud S, Veillon R, Van den Heuvel M, Neal J, Peled N, Früh M, Ng TL, Gounant V, Popat S, Diebold J, Sabari J, Zhu VW, Rothschild SI, Bironzo P, Martinez-Marti A, Curioni-Fontecedro A, Rosell R, Lattuca-Truc M, Wiesweg M, Besse B, Solomon B, Barlesi F, Schouten RD, Wakelee H, Camidge DR, Zalcman G, Novello S, Ou SI, Milia J, Gautschi O. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30:1321-1328.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 433]  [Cited by in F6Publishing: 484]  [Article Influence: 216.5]  [Reference Citation Analysis (0)]
36.  Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15:731-747.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 644]  [Cited by in F6Publishing: 670]  [Article Influence: 214.7]  [Reference Citation Analysis (0)]
37.  Amatu A, Sartore-Bianchi A, Bencardino K, Pizzutilo EG, Tosi F, Siena S. Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer. Ann Oncol. 2019;30:viii5-viii15.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 85]  [Cited by in F6Publishing: 90]  [Article Influence: 28.3]  [Reference Citation Analysis (0)]
38.  Drilon A, Tan DSW, Lassen UN, Leyvraz S, Liu Y, Patel JD, Rosen L, Solomon B, Norenberg R, Dima L, Brega N, Shen L, Moreno V, Kummar S, Lin JJ. Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion-Positive Lung Cancers. JCO Precis Oncol. 2022;6:e2100418.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 5]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
39.  Garrido P, Hladun R, de Álava E, Álvarez R, Bautista F, López-Ríos F, Colomer R, Rojo F. Multidisciplinary consensus on optimising the detection of NTRK gene alterations in tumours. Clin Transl Oncol. 2021;23:1529-1541.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, van Tilburg CM, Nagasubramanian R, Berlin JD, Federman N, Mascarenhas L, Geoerger B, Dowlati A, Pappo AS, Bielack S, Doz F, McDermott R, Patel JD, Schilder RJ, Tahara M, Pfister SM, Witt O, Ladanyi M, Rudzinski ER, Nanda S, Childs BH, Laetsch TW, Hyman DM, Drilon A. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21:531-540.  [PubMed]  [DOI]  [Cited in This Article: ]
41.  Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020;21:271-282.  [PubMed]  [DOI]  [Cited in This Article: ]
42.  Li BT, Ross DS, Aisner DL, Chaft JE, Hsu M, Kako SL, Kris MG, Varella-Garcia M, Arcila ME. HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers. J Thorac Oncol. 2016;11:414-419.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 139]  [Cited by in F6Publishing: 158]  [Article Influence: 19.9]  [Reference Citation Analysis (0)]
43.  Mazières J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, Chouaid C, Wislez M, Diebold J, Felip E, Rouquette I, Milia JD, Gautschi O. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013;31:1997-2003.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 430]  [Cited by in F6Publishing: 478]  [Article Influence: 47.8]  [Reference Citation Analysis (0)]
44.  Kris MG, Camidge DR, Giaccone G, Hida T, Li BT, O'Connell J, Taylor I, Zhang H, Arcila ME, Goldberg Z, Jänne PA. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol. 2015;26:1421-1427.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 194]  [Cited by in F6Publishing: 213]  [Article Influence: 27.7]  [Reference Citation Analysis (0)]
45.  Mazières J, Barlesi F, Filleron T, Besse B, Monnet I, Beau-Faller M, Peters S, Dansin E, Früh M, Pless M, Rosell R, Wislez M, Fournel P, Westeel V, Cappuzzo F, Cortot A, Moro-Sibilot D, Milia J, Gautschi O. Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort. Ann Oncol. 2016;27:281-286.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 195]  [Cited by in F6Publishing: 210]  [Article Influence: 27.9]  [Reference Citation Analysis (0)]
46.  Li B, Gandhi L, Besse B, Jhaveri K, Mazières J, Boni V, Shapiro G, Waqar S, Viteri S, Park H, Quinn D, Stemmer S, Cortot A, Burkard M, Scaltriti M, Won H, Lalani A, McCulloch L, Bebchuk J, Xu F, Bryce R, Meric-Bernstam F, Piha-Paul S, Solit D, Janne P. FP14.15 Neratinib-Based Combination Therapy in HER2-Mutant Lung Adenocarcinomas: Findings from two International Phase 2 Studies. J Thorac Oncol. 2021;16:S234.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
47.  Zhou C, Li X, Wang Q, Gao G, Zhang Y, Chen J, Shu Y, Hu Y, Fan Y, Fang J, Chen G, Zhao J, He J, Wu F, Zou J, Zhu X, Lin X. Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2020;38:2753-2761.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 59]  [Cited by in F6Publishing: 70]  [Article Influence: 29.5]  [Reference Citation Analysis (0)]
48.  SPECTRUM  Spectrum Pharmaceuticals Announces Positive Topline Results in HER2 Exon20 Insertion Mutations from Cohort 2 of the Poziotinib ZENITH20 Trial. [Accessed July 28, 2020]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
49.  Peters S, Stahel R, Bubendorf L, Bonomi P, Villegas A, Kowalski DM, Baik CS, Isla D, Carpeno JC, Garrido P, Rittmeyer A, Tiseo M, Meyenberg C, de Haas S, Lam LH, Lu MW, Stinchcombe TE. Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers. Clin Cancer Res. 2019;25:64-72.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 97]  [Cited by in F6Publishing: 109]  [Article Influence: 24.3]  [Reference Citation Analysis (0)]
50.  Smit EF, Nakagawa K, Nagasaka M, Felip E, Goto Y, Li BT, Pacheco JM, Murakami H, Barlesi F, Saltos AN, Perol M, Udagawa H, Saxena K, Shiga R, Guevara FM, Acharyya S, Shahidi J, Planchard D, Janne PA. Trastuzumab Deruxtecan (T-DXd; DS-8201) in Patients with HER2-mutated Metastatic Non–Small Cell Lung Cancer (NSCLC): Interim Results of DESTINY-Lung01. J Clin Oncol. 2020;38(15_suppl):9504.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 74]  [Cited by in F6Publishing: 75]  [Article Influence: 37.0]  [Reference Citation Analysis (0)]
51.  Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020;382:41-50.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 912]  [Cited by in F6Publishing: 1022]  [Article Influence: 304.0]  [Reference Citation Analysis (0)]
52.  Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:1655-1669.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 248]  [Cited by in F6Publishing: 273]  [Article Influence: 82.7]  [Reference Citation Analysis (0)]
53.  Lamberti G, Andrini E, Sisi M, Rizzo A, Parisi C, Di Federico A, Gelsomino F, Ardizzoni A. Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma. Crit Rev Oncol Hematol. 2020;156:103119.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
54.  Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019;575:217-223.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 843]  [Cited by in F6Publishing: 891]  [Article Influence: 281.0]  [Reference Citation Analysis (0)]
55.  Rolfo C, Cardona AF, Cristofanilli M, Paz-Ares L, Diaz Mochon JJ, Duran I, Raez LE, Russo A, Lorente JA, Malapelle U, Gil-Bazo I, Jantus-Lewintre E, Pauwels P, Mok T, Serrano MJ; ISLB. Challenges and opportunities of cfDNA analysis implementation in clinical practice: Perspective of the International Society of Liquid Biopsy (ISLB). Crit Rev Oncol Hematol. 2020;151:102978.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 49]  [Cited by in F6Publishing: 54]  [Article Influence: 24.5]  [Reference Citation Analysis (0)]