Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

Gastric cancer is common, especially in East Asian countries, and is associated with high recurrence and mortality rates. Currently, there is no standard third-line treatment for metastatic gastric cancer. In this report, we present the case of a 69-year-old man with advanced gastric cancer, whose tumor was negative for human epidermal growth factor receptor 2 (HER2) according to immunohistochemical analysis. Next-generation sequencing performed on paraffin sections of the postoperative tumor samples indicated the presence of the ERBB3 V104L mutation. The patient received irinotecan plus pyrotinib as a third-line therapy and achieved a progression-free survival of 7.6 months with a high quality of life. Therefore, the combined administration of irinotecan and pyrotinib may improve the clinical condition of patients with gastric cancer harboring an ERBB3 mutation. Moreover, ERBB3 could be a potential therapeutic target for gastric cancer.

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