New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib

Abstract 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.

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Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer

OncoTargets and Therapy ◽

10.2147/ott.s34124 ◽

2014 ◽

pp. 841 ◽

Cited By ~ 6

Author(s):

Ying Yuan ◽

Xiao-Fen Li ◽

Jia-Qi Chen ◽

Dong ◽

Shan-Shan Weng ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Critical Appraisal ◽

Locally Advanced ◽

Small Cell ◽

Small Cell Lung

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“My Patient Was Diagnosed With Nontargetable Advanced Non–Small Cell Lung Cancer. What Now?” Diagnosis and Initial Treatment Options for Newly Diagnosed Patients With Advanced NSCLC

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_201231 ◽

2018 ◽

pp. 696-707 ◽

Cited By ~ 3

Author(s):

Melissa Johnson ◽

Nathan A. Pennell ◽

Hossein Borghaei

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Options ◽

The United States ◽

Small Cell ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

Treatment Naïve ◽

Novel Therapeutic Strategies

Although lung cancer remains the leading cause of cancer-related mortality in the United States and worldwide, the rate at which Americans are dying from lung cancer is declining. Improving survival can be explained, in large part, by a growing understanding of the heterogeneous biology of non–small cell lung cancer (NSCLC) as well as recent successes of novel therapeutic strategies more effective and tolerable than platinum-based chemotherapy. We now recognize distinct subtypes of NSCLC, defined by molecular profiling and immunohistochemistry, with different treatment algorithms, including targeted small molecular inhibitors and immunotherapy for each. Both biomarker selection and preferred frontline strategies continue to evolve rapidly, making it difficult for many practitioners to keep up. In this review, we will first describe the recommended initial workup for a patient with advanced or metastatic NSCLC in 2018; next, we present an algorithm to aid oncologists in the selection of the most appropriate therapy for treatment-naive patients with NSCLC, and finally, we offer a look into future treatment options through a discussion of ongoing clinical trials.

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