Treatment patterns and outcomes in early-stage ALK-rearranged non-small cell lung cancer

We evaluated the baseline demographics, treatment patterns, and outcomes of patients with ALK-rearranged early stage (Stage I-III) non-small cell lung cancer (NSCLC). We also evaluated the efficacy and toxicity of durvalumab consolidation treatment in patients with ALK-rearranged unresectable stage III disease. Treatment strategies and PFS of patients with Stage I-III ALK-rearranged NSCLC are similar to patients without molecular driver alterations. Durvalumab consolidation treatment appears generally safe in patients with unresectable stage III ALK-rearranged disease; however, the degree of benefit of such an approach remains unclear. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2022.01.020

Authors: Sabine Schmid, Miguel Garcia, Sierra Cheng, Luna Zhan, Simren Chotai, Karmugi Balaratnam, Khaleeq Khan, Devalben Patel, M. Catherine Brown, Robin Sachdeva, Wei Xua, Frances A. Shepherd, Adrian Sacher, Natasha B. Leighl, Penelope Bradbury, Patrick Moriarty, M. Sara Kuruvilla and Geoffrey Liu

ALK fusion variant 3a/b, concomitant mutations, and high PD-L1 expression were associated with unfavorable clinical response to second-generation ALK TKIs...

Objectives: Second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have significantly improved clinical outcomes in patients with advanced ALK-positive non-small cell lung cancer (NSCLC), but clinical responses vary widely. In this study, the impacts of ALK fusion variants, concomitant mutations, and PD-L1 expression on the clinical response were evaluated in patients receiving second-generation ALK TKIs... Conclusion: ALK fusion variant 3a/b, concomitant mutations, and high PD-L1 expression were associated with unfavorable clinical response to second-generation TKIs in ALK-rearranged NSCLC. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2022.01.006

Authors: Meichen Li, Xue Hou, Jing Chen, Baishen Zhang, Na Wang, Hongyu Han, Likun Chen

Changing ALK-TKI-Resistance Mechanisms in Rebiopsies of ALK-Rearranged NSCLC: ALK- and BRAF-Mutations Followed by Epithelial-Mesenchymal Transition

Anaplastic lymphoma-kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is prone to developing heterogeneous, only partly known mechanisms of resistance to ALK-tyrosine-kinase-inhibitors (ALK-TKIs). We present a case of a 38-year old male, who never smoked with disseminated ALK-rearranged (EML4 (20) – ALK (20) fusion variant 2) lung adenocarcinoma, who received four sequentially different ALK-TKIs and two lines of chemotherapy in-between. We observed significant clinical benefit by the first three ALK-TKIs (Crizotinib, Ceritinib, Alectinib) and chemotherapy with Pemetrexed, resulting in overall survival over 3 years. Longitudinal assessment of progressions by rebiopsies from hepatic metastases showed different mechanisms of resistance to each ALK-TKI, including secondary ALK-mutations and the downstream p.V600E BRAF-mutation that had not been linked to second-generation ALK-TKIs before. Ultimately, in connection with terminal rapid progression and resistance to Alectinib and Lor..... READ ARTICLE

International Journal of Molecular Sciences DOI:10.3390/ijms21082847

Authors: Urbanska, E.M.; Sørensen, J.B.; Melchior, L.C.; Costa, J.C.; Santoni-Rugiu, E.

The efficacy of lorlatinib in a lung adenocarcinoma patient with a novel ALK G1202L mutation: a case report

Report reveals the efficacy of lorlatinib in targeting ALK G1202L and can serve as an option for the clinical management of patients with ALK-rearranged lung adenocarcinoma after acquiring G1202L-mediated resistance from prior ALK inhibitor therapy. Furthermore, it demonstrates the sequential use of crizotinib, brigatinib, and lorlatinib in a patient with advanced ALK-rearranged lung adenocarcinoma with an overall progression-free survival of 33.3 months for the sequential ALK inhibitor regimens. His overall survival was 41.5 months inclusive of all regimens. READ ARTICLE

Cancer Biology & Therapy DOI: 10.1080/15384047.2020.1836947

Authors: Zhaoting Meng, Ting Li, Pei Wang, Analyn Lizaso, Dingzhi Huang

Case StudyKirk SmithDecember 30, 2020TKI Resistance, Lorlatinib, ALK-rearranged NSCLC, ALK G1202L, sequential, ALK inhibitor

174 Poster - Dissecting the landscape of CAF-mediated drug resistance mechanisms in ALK-rearranged NSCLC

Background: Cancer-associated fibroblasts (CAFs) are predominant stromal cells associated with cancer development and drug resistance. Due to the complexity of the crosstalk between CAFs and cancer cells, the underlying mechanism often remains elusive. Here, we aim to elucidate the complex, bidirectional signaling network that governs CAF-mediated resistance to targeted drugs in EML4-ALK-rearranged non-small-cell lung cancer (NSCLC) cells. READ ARTICLE

European Journal of Cancer DOI:10.1016/S0959-8049(20)31205-3

Authors: Q. Hu, L. L. Remsing Rix, X. Li, E. A. Welsh, B. Fang, S. Yun, J. Kroeger, H. R. Lawrence, A. Marusyk, J. M. Koomen, E. B. Haura, U. Rix

Transformation of EML4-ALK fusion-positive adenocarcinoma into squamous cell carcinoma in association with acquired resistance to crizotinib

Background: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. Conclusions: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression. READ ARTICLE

BMC Cancer DOI:10.1186/s12885-019-6486-3

Authors: F. Guisier, N. Piton, M. Bellefleur, N. Delberghe, G. Avenel, E. Angot, O. Vittecoq, M. Ould-Slimane, H. Morisse-Pradier, M. Salaun, L. Thiberville

Case StudyKirk SmithJanuary 6, 2020ALK-rearranged NSCLC, ALK inhibitors, Crizotinib, Ceritinib, Drug toxicity, Osteitis