Patterns of Biomarker Testing Rates and Appropriate Use of Targeted Therapy in the First-Line, Metastatic Non–Small Cell Lung Cancer Treatment Setting

Although the transition to molecularly defined patient subgroups in advanced non-small cell lung cancer (NSCLC) often leads to dramatic and prolonged responses to an inhibitor of an identified oncogenic mutation, acquired resistance eventually ensues. The optimal approach to management in that setting remains the subject of ongoing research, although it is possible to identify several points that distinguish it from traditional tenets based on conventional chemotherapy. Such patients are not equivalent to those who have progressed on first-line chemotherapy, and consideration of initiation of chemotherapy-based regimens as if the patient were being treated first line in the absence of an oncogenic mutation is a reasonable consideration. Acquired resistance is often partial; therefore, continued treatment with the same targeted therapy or another agent against the same target is a strategy favored by many experts, in part to minimize the risk of “rebound progression” that may occur when the targeted therapy is withdrawn. Progression within the central nervous system (CNS) may occur because of poor penetration of the systemic targeted therapy into the CNS, rather than true cellular resistance to the therapy itself; accordingly, local therapy for “brain only” progression with sustained targeted therapy for extracranial disease can be associated with prolonged disease control. Finally, patients with acquired resistance to a targeted therapy are ideal candidates for clinical trials when available, particularly when repeat biopsies of progressing lesions can help elucidate mechanisms of resistance and thereby lead to histologically and molecularly informed treatment decisions.

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First-line therapy for non-small cell lung cancer including targeted therapy: A brief review

Southwest Journal of Pulmonary and Critical Care ◽

10.13175/swjpcc038-18 ◽

2018 ◽

Vol 16 (3) ◽

pp. 157-167 ◽

Cited By ~ 1

Author(s):

Richard Robbins ◽

◽

Thomas Kummet

Keyword(s):

Lung Cancer ◽

Targeted Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

First Line Therapy ◽

Line Therapy

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Impact of adherence to National Comprehensive Cancer Network (NCCN)-recommended first-line therapy on treatment duration for patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21727 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21727-e21727

Author(s):

Ani K John ◽

Baiyu Yang ◽

Roma Shah

Keyword(s):

Lung Cancer ◽

National Comprehensive Cancer Network ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Lower Risk ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Biomarker Testing ◽

Cancer Network

e21727 Background: Identification of molecular alterations can provide essential information to guide personalized treatment selection for advanced non-small cell lung cancer (aNSCLC) patients. However, in routine oncology practice, not all eligible patients receive biomarker testing and receive treatment according to the testing results following the National Comprehensive Cancer Network (NCCN) guideline. We aim to examine the impact of adherence to guideline-recommended therapy on the duration of treatment in a real-world setting. Methods: Patients diagnosed with non-squamous aNSCLC (stage IIIB and above) and received the first-line of therapy (FLOT) between 2011 and 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database were included in this analysis. Adherence was defined as using any NCCN guideline-recommended FLOT consistent with a patient’s biomarker testing results (EGFR, ALK, ROS1, BRAF and PD-L1) assessed up to 90 days before and/or 14 days after the FLOT start date. Non-adherence was defined as not receiving guideline-recommended FLOT based on the above-mentioned biomarker results, or patients treated without evidence of biomarker testing. Median time to treatment discontinuation (TTD) of FLOT was calculated using Kaplan-Meier analysis. Unadjusted and adjusted Cox proportional hazards regression models were used to evaluate the association between guideline adherence and TTD. Results: A total of 17,137 eligible patients were included (67.5% adherent, 32.5% non-adherent). Mean age at diagnosis was 67 years (SD: 10 years). The majority of patients (92%) received care at a community clinic, and 73% reported having insurance plans. Overall, 87.2% had discontinuation of FLOT, including 84.9% in the adherent group and 92.0% in the non-adherent group. The median TTD was 155 days (95% CI 153-159) in the adherent group and 128 days (95% CI 125-132) in the non-adherent group. Adherent patients had a lower risk of FLOT discontinuation in the unadjusted analysis (hazard ratio [HR] 0.78, 95% CI 0.76-0.81), which remained significant after adjusting for potential confounders including age at FLOT start, sex, history of smoking, and stage at initial diagnosis (HR 0.76, 95% CI 0.74-0.79). Conclusions: Among non-squamous aNSCLC patients, the majority of patients were adherent to NCCN guidelines. Adherence was associated with lower risk of discontinuation and longer duration of FLOT.

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