Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology...

Targeted therapy has become essential in the treatment of non-small cell lung cancer (NSCLC). There are currently no guidelines for older patients who are frailer with regard to this type of treatment. Two learned societies, the French Society of Geriatric Oncology (SoFOG) and the French-language Society of Pulmonology (SPLF)/French-language Oncology Group (GOLF), joined forces to conduct a systematic review of the literature from May 2010 to May 2021 regarding the efficacy, toxicity, and feasibility of targeted therapy in older patients with NSCLC. Guidelines were then drawn up to enable clinicians to adapt the type of targeted therapy proposed according to the oncological and geriatric profile of the older patient with NSCLC. READ ARTICLE

Cancers DOI:10.3390/cancers14030769

Authors: Greillier, L.; Gauvrit, M.; Paillaud, E.; Girard, N.; Montégut, C.;
Boulahssass, R.; Wislez, M.; Pamoukdjian, F.; Corre, R.;
Cabart, M.; et al.

Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells

(1) Background: Just little is known about the interaction of ALK/ROS1-targeting kinase inhibitors with ionizing radiation (IR), particularly regarding side effects. We investigated the toxicity in two different lung cell lines both ALK/ROS1 wildtype (healthy and tumor origin) as representatives for normal lung tissue; (2) Methods: Human lung cell line BEAS-2B and malignant A549 lung cancer cells (ALK/ROS1 wt) were treated with alectinib or crizotinib, 2 Gy irradiation or a combination of KI and IR. Cell toxicity was analyzed by cell death (Annexin, 7AAD), colony forming, migration assay and live-cell imaging (TMRM, DRAQ7, Caspase3/7). Cell cycle (Hoechst) were analyzed by flow cytometry; (3) Results: Crizotinib led to higher cell death rates than alectinib, when cells were treated with 10 µM KI. Alectinib induced a more intense growth inhibition of colonies. Both inhibitors showed additive effects in combination with irradiation. Combination treatment (IR + KI) does not lead to synergistic effect on neither cell death nor colony forming; (4) Conclusions: The influence of simultaneous KI and IR was studied in non-mutated ALK/ROS1 cell lines. Both KIs seems to be well tolerated in combination with thoracic radiotherapy and lacked synergistic reinforcement in cellular toxicity. This supports the feasibility of ALK/ROS1 inhibition in combination with thoracic irradiation in future clinical trials. READ ARTICLE

Neoplasia DOI:10.1016/j.neo.2022.100780

Authors: Tina Jost, Ann-Kristin Schultz, Benjamin Frey, Jennifer Vu, Rainer Fietkau, Luitpold V. Distel, Markus Hecht

Review PaperKirk SmithFebruary 1, 2022Lung cells, Alectinib, Crizotinib, Radiotherapy, Normal tissue, Side effects

Analyzing the morphological spectrum of epithelioid fibrous histiocytoma and the immunohistochemical performance of the ALK D5F3 and ALK1 clones

Epithelioid fibrous histiocytoma (EFH) is a cutaneous neoplasm driven by translocations of the anaplastic lymphoma kinase (ALK) gene, which can be demonstrated by immunohistochemical (IHC) analysis. We analyzed the performance of two ALK clones, D5F3 and ALK1, in a cohort of EFHs and described the range of architectural variation of these lesions. TFE3 IHC was performed in ALK-negative EFHs. We identified 21 cases of EFH, 76.2% of which showed an exophytic appearance and 19% displayed flat architecture. A well-developed epidermal collarette was present in 48% of all cases with just more than a third of all the exophytic lesions presenting as dermal-based nodules. ALK D5F3 expression was identified in 76.2% (16/21) of all cases, but only 68.8% were concordantly positive with the ALK1 clone, indicative of a false-negative stain with ALK1 in 31.2% of the cases. For the subset of cases showing positivity for the ALK1 clone, a marked decrease in the percentage of immunolabelled cells was identified when compared with D5F3 (5–50% vs. 100%, respectively). Five cases (23.8%) did not demonstrate ALK expression for either clone, with 3 of those cases showing nuclear positivity for TFE3 IHC and the remaining 2 cases being double negative (ALK-/TFE3-). In summary, we identified that the prototypically described exophytic appearance with epidermal collarette is present in only less than half of the cases. We also demonstrated that the ALK1 antibody is suboptimal in EFH and should not be utilized in this setting. A subset of ALK-negative cases express TFE3, but double-negative cases occur. READ ARTICLE

Human Pathology DOI:10.1016/j.humpath.2021.12.004

Authors: Leila Moayed-Alaei, Ana Cristina Vargas, Dariush Adybeik, Fiona Maclean, Denis Moir

Case StudyKirk SmithFebruary 1, 2022Epithelioid fibrous histiocytoma, ALK, D5F3, ALK1, Clone

YES1 and MYC Amplifications as Synergistic Resistance Mechanisms to Different Generation ALK Tyrosine Kinase Inhibitors in Advanced NSCLC: Brief Report of Clinical and Preclinical Proofs

Introduction: ALK tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced ALK-positive NSCLC. Nevertheless, drug resistance inevitably occurs. Here, we report a case of a patient with metastatic ALK-positive lung adenocarcinoma with an impressive resistance to sequential treatment with ALK TKIs mediated by YES1 and MYC amplification in a contest of epithelial-to-mesenchymal transition and high progressive chromosomal instability... Conclusions: In conclusion, YES1 and MYC amplifications are candidates to justify a rapid acquired resistance to crizotinib entailing primary brigatinib and lorlatinib resistance. In this context, a combination strategy of ALK TKI with dasatinib could be effective to overcome a rapid resistance. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2022.100278

Authors: Roberta Minari, Samuel Valentini, Denise Madeddu, Andrea Cavazzoni, Silvia La Monica, Costanza Anna Maria Lagrasta, Roberto Bertorelli, Veronica De Sanctis, Paola Fassan, Cinzia Azzoni, Lorena Bottarelli, Caterina Frati, Letizia Gnetti, Francesco Facchinetti, Pier Giorgio Petronini, Roberta Alfieri, Alessandro Romanel, Marcello Tiseo

Case StudyKirk SmithFebruary 1, 2022NSCLC, ALK TKIs, Resistance mechanism, YES1 amplification, MYC amplification

Deep RNA Sequencing Revealed Fusion Junctional Heterogeneity May Predict Crizotinib Treatment Efficacy in ALK-Rearranged NSCLC

Introduction: Gene fusion variants in ALK-rearranged NSCLC may predict patient outcomes, but previous results have been inconclusive. Fusion isoforms coexisting in the same tumor may affect the efficacy of targeted therapy, but they have not been investigated... Conclusions: Intratumoral EML4-ALK isoforms may predict the efficacy of targeted therapy in ALK-rearranged NSCLC. Temporal changes of intratumoral fusion isoforms may result from differential selection pressures that a drug might have on one isoform over another. Larger studies on fusion heterogeneity using RNA sequencing are warranted. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.09.016

Authors: Zhengbo Song, Shifeng Lian, Silvia Mak, Maggie Zi-Ying Chow, Chunwei Xu, Wenxian Wang, Hoi Yee Keung, Chenyu Lu, Firaol Tamiru Kebede, Yanqiu Gao, Wah Cheuk, William Chi Shing Cho, Mengsu Yang, Zongli Zheng

ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data

We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients. Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT). At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of..... READ ARTICLE

The Oncologist DOI:10.1093/oncolo/oyab005

Authors: Moskovitz, Mor, Dudnik, Elizabeth, Shamai, Sivan, Rotenberg, Yakir, Popovich-Hadari, Noa, Wollner, Mira, Zer, Alona, Gottfried, Maya, Mishaeli, Moshe, Rosenberg, Shoshana Keren, Onn, Amir, Merimsky, Ofer, Urban, Damien, Peled, Nir, Maimon, Natalie, Bar, Jair

Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial

WX-0593 (Iruplinalkib) is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor (TKI). In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer (NSCLC) patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety assessed by investigators. In the dose-expansion phase, the primary endpoint was objective response rate (ORR) assessed by investigators. Between September 25, 2017 and October 15, 2018, a total of 153 patients received WX-0593 treatment. Two dose-limiting toxicities (DLTs) including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient. MTD was not rea..... READ ARTICLE

Signal Transduction and Targeted Therapy DOI:10.1038/s41392-021-00841-8

Authors: Shi, Y., Fang, J., Hao, X. et al.

Histological and Molecular Plasticity of ALK-positive Non-Small-Cell Lung Cancer under Targeted Therapy - a Case Report

With medical progress in cancer therapy, tyrosine kinase inhibitors (TKIs) became a standard of care for many cancer types. But the broad range of possible targeted therapies was accompanied by a plethora of potential resistance mechanisms, of which many have still to be identified. Here, we present the case of a patient with an EML4-ALK translocated non-small-cell lung cancer treated with four different TKIs. His tumor developed not only a well-known ALK-TKI resistance mutation, but also underwent a histological transformation from adenocarcinoma to squamous cell carcinoma. To confirm a shared monoclonal origin of the phenotypically different tumors, a phylogenetic reconstruction was conducted: this revealed a cluster of mutations including NFE2L2, KMT2D and MLH1 which are possible triggering events for the transformation. READ ARTICLE

Cold Spring Harbor Molecular Case Studies DOI:10.1101/mcs.a006156

Authors: Markus Ball, Petros Christopoulos, Martina Kirchner, Michael Allgaeuer, Regine Brandt, Hauke Winter, Claus Peter Heussel, Felix Herth, Stefan Froehling, Rajkumar Savai, Mark Kriegsmann, Peter Schirmacher, Solange Peters, Michael Thomas, Albrecht Stenzinger, Daniel Kazdal

Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Central nervous system (CNS) metastases in patients with ALK-positive non-small cell lung cancer (NSCLC) are a cause of substantial morbidity and mortality. Although alectinib had demonstrated promising intracranial efficacy in several clinical trials, data were limited on its CNS activity in real-world settings. Our study substantiated the potent CNS activity of alectinib in real-world settings. Patients with symptomatic and asymptomatic BM could benefit from alectinib comparatively, which indicated that alectinib alone might defer the timing of local treatment. However, our results should be treated cautiously owing to limited sample size. READ ARTICLE

BMC Med DOI:10.1186/s12916-021-02207-x

Authors: Zou Z, Xing P, Hao X, Wang Y, Song X, Shan L, Zhang C, Liu Z, Ma K, Dong G, Li J.

HER3 activation contributes toward the emergence of ALK inhibitor-tolerant cells in ALK-rearranged lung cancer with mesenchymal features

Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have shown dramatic efficacy in patients with ALK-rearranged lung cancer; however, complete response in these patients is rare. Here, we investigated the molecular mechanisms underlying the emergence and maintenance of drug-tolerant cells in ALK-rearranged lung cancer. Cell based-assays demonstrated that HER3 activation and mesenchymal-to-epithelial transition, mediated through ZEB1 proteins, help maintain cell survival and induce the emergence of ALK-TKI-tolerant cells. Compared with ALK-TKIs alone, cotreatment with pan-HER inhibitor afatinib and ALK-TKIs prevented tumor regrowth, leading to the eradication of tumors in ALK-rearranged tumors with mesenchymal features. Moreover, pre-treatment vimentin expression in clinical specimens obtained from patients with ALK-rearranged lung cancer was associated with poor ALK-TKI treatment outcomes. These results demonstrated that HER3 activation plays a pivotal role in the emergence of ALK-TKI-tolerant cells. Furthermore, the inhibition of HER3 signals combined with ALK-TKIs dramatically improves treatment outcomes for ALK-rearranged lung cancer with mesenchymal features. READ ARTICLE

Precision Oncology DOI:10.1038/s41698-021-00250-8

Authors: Keiko Tanimura, Tadaaki Yamada, Koutaroh Okada, Kunihiro Nakai, Mano Horinaka, Yuki Katayama, Kenji Morimoto, Yuri Ogura, Takayuki Takeda, Shinsuke Shiotsu, Kosuke Ichikawa, Satoshi Watanabe, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Hirokazu Taniguchi, Kazue Yoneda, Satoaki Matoba, Toshiyuki Sakai, Hisanori Uehara, Seiji Yano, Tetsuro Kusaba, Ryohei Katayama, Koichi Takayama

Pre-ClinicalKirk SmithJanuary 18, 2022Non-small-cell lung cancer, Translational research

Assessment of ALK Fusions in Uncommon Inflammatory Myofibroblastic Tumors With ALK IHC Positivity but FISH-Equivocal Findings by Targeted RNA Sequencing

Context: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are common methods to detect ALK status in inflammatory myofibroblastic tumors (IMTs). However, equivocal ALK FISH signals and inconsistency between FISH and IHC are occasionally observed. Objective: To study the inconsistency between FISH and IHC, and clarify ALK status in IMT by targeted RNA sequencing (RNAseq). Conclusions: These findings indicated that RNAseq can simultaneously detect multiple gene fusions and provide fusion forms and breakpoints, which is of great value for differential diagnosis, especially for those uncommon IMTs with equivocal FISH findings, or inconsistency between IHC and FISH. READ ARTICLE

Archives of Pathology & Laboratory Medicine DOI:10.5858/arpa.2021-0230-OA

Authors: Qianlan Yao, Qianming Bai, Xin Zhang, Gang Ji, Heng Chang, Xu Cai, Lin Yu, Jian Wang, Xiaoli Zhu, Xiaoyan Zhou

Continuation of Lorlatinib in ALK-positive NSCLC Beyond Progressive Disease

Retrospective analyses in the ongoing phase II trial (NCT01970865) investigated clinical benefit of continuing lorlatinib beyond progressive disease (LBPD). Patients with prior crizotinib as the only ALK TKI were Group A (n = 28); those with ≥1 prior second-generation ALK TKIs were Group B (n = 74). LBPD was defined as >3 weeks of lorlatinib treatment after investigator-assessed progressive disease. Only patients with a best overall response of complete or partial response or stable disease were included.
There were no major differences in baseline characteristics between groups. Median duration of treatment for LBPD patients was 32.4 months (Group A) and 16.4 months (Group B) versus 12.5 months (Group A) and 7.7 months (Group B) for non-LBPD patients. Median overall survival (OS) in Group A was not reached (NR) in LBPD patients versus 24.4 months (95% confidence interval [CI] 12.1-NR); Group B median was 26.5 months (95% CI 18.7-35.5) in LBPD patients versus 14.7 months (95% CI 9.3-38..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/ j.jtho.2021.12.011

Authors: Ou S-HI, Solomon BJ, Shaw AT, Gadgeel SM, Besse B, Soo RA, Abbattista A, Toffalorio F, Wiltshire R, Bearz A

Kirk SmithJanuary 14, 2022

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involv..... READ ARTICLE

Blood DOI:10.1182/blood.2021013338

Authors: Paul G. Kemps, Jennifer Picarsic, Benjamin H. Durham, Zofia Hélias-Rodzewicz, Laura Hiemcke-Jiwa, Cor van den Bos, Marianne D. van de Wetering, Carel J. M. van Noesel, Jan A. M. van Laar, Robert M. Verdijk, Uta E. Flucke, Pancras C. W. Hogendoorn, F. J. Sherida H. Woei-A-Jin, Raf Sciot, Andreas Beilken, Friedrich Feuerhake, Martin Ebinger, Robert Möhle, Falko Fend, Antje Bornemann, Verena Wiegering, Karen Ernestus, Tina Méry, Olga Gryniewicz-Kwiatkowska, Bozenna Dembowska-Baginska, Dmitry A. Evseev, Vsevolod Potapenko, Vadim V. Baykov, Stefania Gaspari, Sabrina Rossi, Marco Gessi, Gianpiero Tamburrini, Sébastien Héritier, Jean Donadieu, Jacinthe Bonneau-Lagacherie, Claire Lamaison, Laure Farnault, Sylvie Fraitag, Marie-Laure Jullié, Julien Haroche, Matthew Collin, Jackie Allotey, Majid Madni, Kerry Turner, Susan Picton, Pasquale M. Barbaro, Alysa Poulin, Ingrid S. Tam, Dina El Demellawy, Brianna Empringham, James A. Whitlock, Aditya Raghunathan, Amy A. Swanson, Mariko Suchi, Jon M. Brandt, Nabeel R. Yaseen, Joanna L. Weinstein, Irem Eldem, Bryan A. Sisk, Vaishnavi Sridhar, Mandy Atkinson, Lucas R. Massoth, Jason L. Hornick, Sanda Alexandrescu, Kee Kiat Yeo, Kseniya Petrova-Drus, Stephen Z. Peeke, Laura S. Muñoz-Arcos, Daniel G. Leino, David D. Grier, Robert Lorsbach, Somak Roy, Ashish R. Kumar, Shipra Garg, Nishant Tiwari, Kristian T. Schafernak, Michael M. Henry, Astrid G. S. van Halteren, Oussama Abla, Eli L. Diamond, Jean-François Emile

Multiplex fluorescence in situ hybridization testing for anaplastic lymphoma kinase and c-ros oncogene 1 gene rearrangements on cytology smears in lung adenocarcinomas:..

Introduction: Multiplex anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) fluorescence in situ hybridization (FISH) probes conserve tissue by analyzing both ALK and ROS1 gene rearrangements (ALK-R/ROS1-R) in a single test. The positivity cutoffs have been validated on formalin-fixed, paraffin-embedded (FFPE) tissue sections and not tested on non–cell block (CB) cytology preparations. We sought to validate non-CB cytology preparations for the detection of ALK-R/ROS1-R using multiplex ALK/ROS1 FISH probes by comparing the results with matched FFPE results... Conclusions: Non-CB cytology smears are highly suitable for multiplex FISH analysis with 100% concordance with FFPE FISH and/or ALK D5F3 companion diagnostics assay results. READ ARTICLE

Journal of the American Society of Cytopathology DOI:10.1016/j.jasc.2022.01.001

Authors: Aruna Nambirajan, Deeksha Rana, Komal Samant, Aswini Prabakaran, Prabhat Malik, Deepali Jain

Review PaperKirk SmithJanuary 13, 2022ALK, ROS1, Multiplex FISH, Cytology smear, Lung adenocarcinoma

Continuation of Lorlatinib in ALK-positive NSCLC Beyond Progressive Disease

Continuing LBPD is a viable treatment option for select patients with ALK-positive NSCLC who progressed on lorlatinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.12.011

Authors: Sai-Hong I.Ou, Benjamin J.Solomon, Alice T.Shaw, Shirish M.Gadgeel, BenjaminBesse, Ross A.Soo, Antonello Abbattista, Francesca Toffalorio, Robin Wiltshire, Alessandra Bearz

Clinical TrialsKirk SmithJanuary 10, 2022lorlatinib, NSCLC, post-progression treatment, RECIST 1.1

[Anaplastic lymphoma kinase-translocation renal cell carcinoma: clinical and pathological analysis]

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma. READ ARTICLE

Zhonghua Bing Li Xue Za Zhi DOI:10.3760/cma.j.cn112151-20210323-00227

Authors: S H Di, X T Wang, Q Y Xia, Z F Lu, H H Ma, R S Zhang, X Wang, Q Rao

[Anaplastic lymphoma kinase-translocation renal cell carcinoma: clinical and pathological analysis]

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma. READ ARTICLE

Zhonghua Bing Li Xue Za Zhi DOI:10.3760/cma.j.cn112151-20210323-00227

Authors: S H Di, X T Wang, Q Y Xia, Z F Lu, H H Ma, R S Zhang, X Wang, Q Rao

Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations

Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the new classification paradigm of non–small-cell lung cancer is further characterized by molecularly defined subsets actionable with targeted therapies and the treatment landscape is becoming increasingly complex. This review encompasses the current standards of care for targeted therapies in lung cancer with driver molecular alterations. Targeted therapies for EGFR exon 19 deletion and L858R mutations, and ALK and ROS1 rearrangements are well established. However, there is an expanding list of approved targeted therapies including for BRAF V600E, EGFR exon 20 insertion, and KRAS G12C mutations, MET exon 14 alterations, and NTRK and RET rearrangements. In addition, there are numerous other oncogenic drivers, such as HER2 exon 20 insertion mutations, for wh..... READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.21.01626

Authors: Aaron C. Tan and Daniel S. W. Tan

Review PaperKirk SmithJanuary 5, 2022targetable oncogenic driver, precision oncology

Case Report: A Novel Non-Reciprocal ALK Fusion: ALK-GCA and EML4-ALK Were Identified in Lung Adenocarcinoma, Which May Respond to Alectinib Adjuvant-Targeted Therapy

Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancers (NSCLCs) have favorable and impressive response to ALK tyrosine kinase inhibitors (TKIs). However, ALK rearrangement had approximately 90 distinct fusion partners. Patients with different ALK fusions might have distinct responses to different-generation ALK-TKIs. In this case report, we identified a novel non-reciprocal ALK fusion: ALK-grancalcin (GCA) (A19: intragenic) and EML4-ALK (E20: A20) by next-generation sequencing (NGS) in a male lung adenocarcinoma patient who was staged as IIIB-N2 after surgery. After a multidisciplinary discussion, the patient received alectinib adjuvant targeted therapy and postoperative radiotherapy (PORT). He is currently in good condition, and disease-free survival (DFS) has been 20 months so far, which has been longer than the median survival time of IIIB NSCLC patients. Our study extended the spectrum of ALK fusion partners in ALK + NSCLC, and we reported a new ALK fusion: ALK-GCA a..... READ ARTICLE

Frontiers in Oncology DOI:10.3389/fonc.2021.782682

Authors: Zhai Xiaoqian, Wu Qiang, Pu Dan, Yin Liyuan, Wang Weiya, Zhu Daxing, Xu Feng

Case StudyKirk SmithJanuary 5, 2022ALK-GCA, EML4-ALK, Alectinib, non-reciprocal ALK rearrangement

Short communication: The activity of brigatinib in patients with disease progression after next generation anaplastic lymphoma tyrosine kinase inhibitors...

Highlights:
- Brigatinib demonstrated activity in patients with disease progression after next-generation anaplastic lymphoma (ALK) tyrosine kinase inhibitors (TKI’s).
- The objective response was similar in patients who received next generation ALK inhibitors as first-line or second line therapy, and patients with and without brain metastases at baseline.
- Circulating tumor DNA testing (ctDNA) for ALK resistance mutations is feasible; however, a number of patients did not have detectable ctDNA or an ALK resistance mutations. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.12.019

Authors: Thomas E. Stinchcombe, Xiaofei Wang, Robert C. Doebele, Leylah M. Drusbosky, David E. Gerber, Leora Horn, Erin M. Bertino, Geoff Liu, Liza C. Villaruz, D. Ross Camidge

Clinical TrialsKirk SmithJanuary 3, 2022Targeted therapy, biomarker, ctDNA, liquid biopsy