Abstract
Simple SummaryThe growing efficacy and availability of new targeted systemic therapies have markedly improved the prognosis of metastatic lung cancer patients harboring ALK rearrangements. The use of effective targeted therapies capable of maintaining a prolonged control of disease, for as long as possible, is paramount to ensure the best survival outcomes. In this regard, in cases of oligoprogression, “beyond progression” systemic treatment added to local ablative therapies is considered a feasible option in an attempt to improve the quality and quantity of patients’ lives, even if based on retrospective data. Certainly, treatment of ALK rearranged lung cancer patients with oligoprogressive disease must be individualized and based on multidisciplinary decisions. Above all, when further molecular targeted therapies are available, options must always be evaluated, especially in case of cerebral progression. In this review, we provide an updated and comprehensive overview of the main treatment strategies in cases of ALK rearranged oligoprogression.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.
Highlights
We report a real-world clinical story that supports the importance of multidisciplinary involvement and discussion in oncogene-addicted patients with an oligoprogressive disease
In 1995, Hellman and Weichselbaum first introduced the concept of oligometastatic disease (OMD), an intermediate state between localized and widespread tumor in which metastases are limited in number and location; compared with more advanced stages, OMD is more indolent and it is more amenable to ablative therapy for metastatic lesions [6]
Reported longer intracranial time to progression in patients who received sequential treatment with a second anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), including either ceritinib, alectinib, brigatinib or PLB1003, compared with those treated beyond progression after radiotherapy (p = 0.003) [33]
Summary
Several types of ALK translocation have been discovered, all resulting from the fusion between ALK gene portion encoding for the intracellular tyrosine kinase domain (exons 20–29) and different partners, of which echinoderm microtubule-associated protein like-4 (EML4) is involved in 90% of cases. This leads to the production of a chimeric protein with a constitutive tyrosine–kinase activity responsible for uncontrolled cellular proliferation [2]. In this context, extending the benefit deriving from targeted treatment is paramount, above all when disease progression occurs in a limited number of sites, defining the so-called oligoprogressive state. We report a real-world clinical story that supports the importance of multidisciplinary involvement and discussion in oncogene-addicted patients with an oligoprogressive disease
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