Abstract
BackgroundMost non‐small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase‐tyrosine kinase inhibitor (ALK‐TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK‐TKI therapies; however, little clinical data exists on the clinical efficacy of ALK‐TKI tailored to secondary mutation.MethodsA retrospective study was conducted to analyze the patterns of ALK‐TKI treatment and clinical outcomes, including progression free survival (PFS), of ALK‐positive NSCLC patients who received rebiopsy. Based on the rebiopsy results, secondary mutations in the ALK gene that were shown to be associated with the efficacy of ALK‐TKI therapy in the preclinical or clinical setting were defined as “sensitive mutations (SM)”.ResultsAmong 71 patients who received ALK‐TKI for NSCLC at our institution, 20 patients received rebiopsy, and secondary SM were found in eight patients. The objective response rate (ORR) of the cases with SM who received ALK‐TKI therapy was 88.9%, while the ORR of the patients without SM who received ALK TKI or chemotherapy was 20.0%; however, the PFS of the patients with SM was relatively short (with SM vs. without SM: 5.6 months vs. 5.1 months).ConclusionsThe selection of ALK‐TKI based on the rebiopsy result was associated with a high ORR and relatively short PFS. The mechanism responsible for the short PFS of sensitive ALK‐TKI to secondary mutation should be clarified.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide
Previous studies have reported that rebiopsy could provide further information, including histological or genetic changes that might be helpful in optimizing the treatment[24,25]; little clinical data exists regarding the prognostic impact of rebiopsy on anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients
We evaluated the treatment course and clinical efficacy of anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) in ALKpositive NSCLC patients who received rebiopsy after relapse on ALK-TKI, and the administration of ALK-TKIs based on the secondary sensitive mutations was associated with a high objective response rate (ORR) and relatively short progression free survival (PFS) (87.5% and 5.4 months, respectively)
Summary
Lung cancer is the leading cause of cancer-related death worldwide. Recent advances in chemotherapy and molecular targeted therapy have led to the remarkable improvement of survival of lung cancer patients, especially those with non-small cell lung cancer (NSCLC). The superiority of crizotinib, a first generation ALK-tyrosine kinase inhibitor (ALK-TKI), to standard chemotherapy has been demonstrated in patients with ALK-positive advanced NSCLC previously treated with platinum-based chemotherapy.[1]. Even if patients initially respond well to ALK-TKI, the majority eventually experience disease progression due to various mechanisms, including secondary mutations within the ALK tyrosine kinase domain and activation of alternative signaling pathways.[4,16–25]. Most non-small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) therapy because of acquired resistance. Based on the rebiopsy results, secondary mutations in the ALK gene that were shown to be associated with the efficacy of ALK-TKI therapy in the preclinical or clinical setting were defined as “sensitive mutations (SM)”. Conclusions: The selection of ALK-TKI based on the rebiopsy result was associated with a high ORR and relatively short PFS. The mechanism responsible for the short PFS of sensitive ALK-TKI to secondary mutation should be clarified
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