Anaplastic Lymphoma Kinase-Positive Lung Cancer with Mucoepidermoid Carcinoma Differentiation: A Case Report

Mucoepidermoid carcinoma (MEC) of the lung is an extremely rare tumor, and a standard chemotherapy has not been established. Furthermore, little work has been conducted on the genetic characteristics of MEC. We herein report the case of a 42-year-old nonsmoking male patient who was referred to our hospital due to cough. Chest computed tomography demonstrated infiltration and atelectasis in the right lower lobe. He was eventually diagnosed with non small cell lung cancer (NSCLC) with MEC differentiation corresponding to clinical stage IVA (cT4N2M1a[PLE]). Genetic testing for EGFR mutations was negative, but positive for anaplastic lymphoma kinase (ALK) fusion gene. After 2 weeks of first-line treatment with alectinib, the tumor decreased in size and his symptoms improved. Advanced MEC is a rare tumor, and reports on the treatment of ALK-positive NSCLC with MEC differentiation are rare. READ ARTICLE

Case Reports in Oncology DOI:10.1159/000510042

Authors: Sakatani T., Masuda Y., Morikawa T., Usui K

Case StudyKirk SmithAugust 30, 2020Mucoepidermoid carcinoma, MEC, nonsmoking, male, ALK positive, alectinib

$TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors$

TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors

Anaplastic lymphoma kinase (ALK) gene rearrangements occur in up to 7% of patients with non-small cell lung cancer (NSCLC) with the majority as EML4-ALK fusions. Crizotinib (first generation ALK inhibitor) was the first approved ALK inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer. However, development of resistance to crizotinib caused by secondary kinase domain mutations, bypass signaling, or morphology changes occurs. Second generation ALK inhibitors alectinib, ceritinib, and brigatinib were able to overcome the majority of ALK resistant mutations (L1196M, G1269A and F1174L) acquired with crizotinib. The solvent front mutation (SFM) G1202R is a common resistant mutation to crizotinib and the second generation ALK inhibitors. Lorlatinib, a third generation ALK inhibitor, can overcome G1202R resistance with moderate IC50 values of 40 - 60 nM in cell-based assays. Although, compound mutations such as ones with both gatekeeper and solvent front mutations..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-5226

Authors: J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee and Brion Murray

Conference PaperKirk SmithAugust 1, 2020ALK, EML4-ALK fusions, NSCLC, ALK positive, TPX-0131

Brigatinib in Japanese ALK positive NSCLC patients previously treated with ALK tyrosine kinase inhibitors: J-ALTA

Background: Brigatinib is an ALK inhibitor with demonstrated activity against ALK resistance mutations. To evaluate efficacy and safety in Japanese patients with ALK-positive non-small cell lung cancer (NSCLC), a prospective, single-arm, phase 2 study was conducted. We report the efficacy and safety of brigatinib in patients who have progressed on alectinib with or without prior crizotinib and of those who previously received up to two ALK tyrosine kinase inhibitors (TKIs) with or without prior chemotherapy... Conclusions: Brigatinib showed clinically meaningful efficacy in Japanese patients refractory to prior alectinib (first line or post crizotinib), regardless of prior chemotherapy. The safety profile of brigatinib was consistent with prior studies and no new safety findings were identified. Clinical trial information: NCT03410108 READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.9537

Authors: Tatsuya Yoshida, Makoto Nishio, Toru Kumagai, Toyoaki Hida, Ryo Toyozawa, Tadasuke Shimokawaji, Koichi Goto, Kazuhiko Nakagawa, Yuichiro Ohe, Nobuyuki Yamamoto, Kentarou Kudou, Takayuki Asato, Pingkuan Zhang, Takashi Seto

P114-15 Lorlatinib in ALK- or ROS1-Positive Non-Small Cell Lung Cancer Patients: Experience from an Early Access Program in Turkey

The aim of this study is to evaluate the efficacy and safety of lorlatinib in an Expanded Access Program (EAP) in Turkey.The EAP was open-label, multicenter, and single-arm. Patients were eligible to receive lorlatinib (100 mg p.o/day) if they had advanced stage ALK- or ROS1-positive NSCLC and had progressed on crizotinib and/or second generation ALK inhibitors such as ceritinib or alectinib. The primary endpoint was PFS with lorlatinib. Secondary endpoints were objective response rate, overall survival, and safety. In this EAP, lorlatinib showed systemic activity in patients with advanced ALK+ or ROS1+ NSCLC, regardless of CNS metastases and previous TKI treatment. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1166

Authors: S. Kilickap, U. Demirci, F. Bugdayci, D. Tural, T. Korkmaz, S. Paydas, C. Yilmaz, H. Turna, A. Sezer, H. Yesil Cinkir, K. Okutur, M. Erman, Y. Eralp, D. Cabuk, A. Isikdogan, A. Demirkazik, A. Karaoglu, D. Yazilitas, F. Cay Senler, P.F. Yumuk, H. Coskun, I. Yildiz, I. Oztop, I. Beypinar, K. Aydin, M. Kaplan, N. Meydan, O.F. Olmez, O. Ozyilkan, S. Seber, C. Arslan, M.A. Sendur, I. Cicin

EP101-35 Concurrent Use of Low Dose Aspirin and Vitamin D in ALK, ROS and EGFR Mutant NSCLC: A Single Institution Retrospective Analysis

Recent meta-analysis published by Feng et al. analyzed seventeen studies and reported statistically significant reduction in risk of lung cancer by 8% when circulating 25-VD is at 10 nmol/L, this benefit was seen in both Caucasian and Asian population. To our knowledge, there have been no studies looking at influence of concurrent vitamin D or aspirin intake on outcomes in ALK, ROS and EGFR pos NSCLC treated with tyrosine kinase inhibitors. We performed a retrospective single institution analysis to study this association.Patients (pts) with ALK, ROS EGFR pos NSCLC treated with first line TKI from January 2014 to June 2017 were included. Information on concurrent use and doses of aspirin and vitamin D supplements were studied. Patients were dichotomized based on use of these individual supportive medications. Two sample t-test was used to compare mean PFS and chi-square test to compare proportions of disease control rate (DCR) at 3 months between groups.Our study did not show any diffe..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2008

Authors: C. Bernabe, S. Sharma, J. Sanchez, K. Sullivan, N. Seetharamu

Conference PaperKirk SmithOctober 1, 2019PFS, DCR, EGFR, ROS, ALK positive, NSCLC, vitamin D, aspirin, TKI

Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib

Objectives: Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC. Conclusions: Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib. READ ARTICLE

Lung Cancer: 10.1016/j.lungcan.2019.05.025

Authors: Niamh Coleman, Andrew Wotherspoon, Nadia Yousaf, Sanjay Popat