<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

Abstract

The treatment of advanced non-small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade. Molecular characterization of the disease has led to the rapid development of personalized medicine and swift delivery of targeted therapies to patients. The discovery of the anaplastic lymphoma kinase (ALK) gene in patients with NSCLC has resulted in rapid bench-bedside transition of several active drugs, with several others currently in clinical trials. After the first-generation ALK inhibitor crizotinib, nextgeneration ALK inhibitors have entered clinical applications for ALK-rearranged NSCLC. Ceritinib, alectinib, and brigatinib have all received approval for ALK-positive patients who have failed prior crizotinib, as well as first-line therapy in treatment-naïve patients based on favorable efficacy. Most recently, lorlatinib, a potent, newer-generation ALK inhibitor, has been approved as second-or third-line treatment. These advances have led to better patient outcomes, but concurrently have led to several crucial unanswered questions about optimal care for ALK-positive NSCLC patients. The ultimate acquisition of resistance to ALKinhibitor therapy poses a challenge to ongoing research efforts, in addition to the routine management of these patients in the clinic. This review provides a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlights current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC.

Validation of the ALK-Brain Prognostic Index for patients with ALK-rearranged lung cancer and brain metastases

“…Our findings underscore the need for prospective and multicentric validation of the proposed prognostic score, in particular under the inclusion of more patients treated with the newer next-generation ALK-TKIs that have improved brain efficacy and are preferred for the initial patient treatment currently. 3 , 18 , 19 One future step could also be the enrichment of prognostic algorithms with molecular tumor features, such as the presence of the shorter and more oncogenic EML4-ALK fusion variant 3, which has been associated with earlier intracranial progression in TKI-treated ALK+ NSCLC. 10 …”

Emerging trends of therapy related myeloid neoplasms following modern cancer therapeutics in the United States

“…In the most recent period (2011–2016), we noted a decline in tAML risk after early stage (regional but not localized) NSCLC. Targeted therapies ( EGFR/ALK -TKIs) and ICIs have revolutionized treatment of advanced NSCLC and about 25% of NSCLC patients can harbor EGFR and ALK mutations 9 , but these were not approved for early stage NSCLC during periods of our study. Therefore, decrease in tAML risk after regional stage NSCLC in the most recent period is rather surprising.…”

“…Modern targeted and immune therapeutics for cancer have revolutionized the field of oncology. Specifically, treatments for non-small cell lung cancer [NSCLC; small molecule pathway inhibitors 8 , 9 and immune checkpoint inhibitors] 10 , RCC [small molecule and immune checkpoint inhibitors] 11 , melanoma [immunotherapy with cytokines, checkpoint inhibitors and small molecule inhibitors] 12 and multiple myeloma [MM; immunomodulatory drugs (IMiDs) such as lenalidomide 13 , proteasome inhibitors and monoclonal antibodies] 14 have evolved considerably ( Supplemental Table and sFig. 1 ).…”

6th Molecular Oncology Society Conference: Improving patient survival by molecularly targeted therapies

“…Alectinib provides the longest duration of disease control along with a defined treatment sequence, improving the prognosis for patients with advanced ALK+ NSCLC. [17] Topics on "Genitourinary Cancer" were chaired by Dr. Maheboob Basade and Dr. Shailesh Talati. The roles of rucaparib in metastatic castration-resistant prostate cancer (mCRPC) with HRR gene alterations were discussed by Dr. Chaitanya Krishna.…”