Management of Oligoprogression in Patients with Metastatic NSCLC Harboring ALK Rearrangements

Abstract

Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene-addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all, when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, a multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the site of disease progression, in order to improve not only survival, but also quality of life. In this review we provide an updated and comprehensive overview of the main treatment strategies in cases of ALK rearranged oligoprogression, including systemic treatment as well as local therapy, and report a real-world clinical story, with the final aim of identifying the most promising management for this subset of patients.

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations

“…Oncogenic receptor tyrosine kinases are definitive drug therapy targets for the treatment of NSCLC patients containing gene mutations, especially EGFR mutations and ALK rearrangements that are targets of the precision medicine management of chest neoplasms [ 149 , 150 ]. A meta-data analysis showed that individuals who never smoked were more susceptible to the EGFR and ALK-EML4 mutations than ever-smokers [ 3 ].…”

Alectinib continuation beyond progression in ALK-positive non-small cell lung cancer with alectinib-refractory

“…Furthermore, the Asian population-based ALESIA study showed even better efficacy, with an mPFS of 41.6 months and an ORR of 91%. However, despite the significant clinical benefits achieved with alectinib, resistance to alectinib occurred in 53.3% of patients treated with alectinib as the first-line therapy, leading to disease progression, and more progressive disease occurred in second-line alectinib treatment ( 4 , 15 - 17 ). ALK-TKIs resistance mainly arises from ALK mutations and ALK amplification, such as the G1202R mutation ( 18 ).…”

“…Subsequent therapeutic decision-making will be based firstly on the type of progression and secondly on the mechanism of resistance ( 4 , 21 ). Progression can be divided into oligoprogression, central nervous system (CNS) progression, and systemic progression ( 4 , 17 ). Oligoprogression is defined as a tumor disease that progresses in a limited number of sites ( 17 ).…”

“…Progression can be divided into oligoprogression, central nervous system (CNS) progression, and systemic progression ( 4 , 17 ). Oligoprogression is defined as a tumor disease that progresses in a limited number of sites ( 17 ). CNS progression is defined as progression involving only the CNS.…”

“…CNS progression is defined as progression involving only the CNS. When the disease suffers progression in more sites, it is defined as systemic progression ( 17 ). It can be considered that oligoprogression or CNS progression does not necessarily indicate a complete failure of the prior TKI treatment, it may be due to heterogeneity within and between tumors.…”