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. 2024 Jan;20(1):145-153.
doi: 10.1200/OP.22.00611. Epub 2023 Aug 9.

Compromised Outcomes in Stage IV Non-Small-Cell Lung Cancer With Actionable Mutations Initially Treated Without Tyrosine Kinase Inhibitors: A Retrospective Analysis of Real-World Data

Jeffrey A Scott  1 , Jochen Lennerz  2 , Melissa Lynne Johnson  3 , Lucio N Gordan  4 , Robert H Dumanois  5 , Luca Quagliata  5 , Lauren L Ritterhouse  2 , Federico Cappuzzo  6 , Brandon Wang  1 , Mei Xue  1 , Anupama Vasudevan  1 , Prateesh Varughese  1 , Varun Vaidya  7 , Mike Gart  1 , Natalie Dorrow  1 , Hinco J Gierman  1 , Rushir J Choksi  8
Affiliations

Compromised Outcomes in Stage IV Non-Small-Cell Lung Cancer With Actionable Mutations Initially Treated Without Tyrosine Kinase Inhibitors: A Retrospective Analysis of Real-World Data

Jeffrey A Scott et al. JCO Oncol Pract. 2024 Jan.

Abstract

Purpose: Identification and targeting of actionable oncogenic drivers (AODs) in advanced non-small-cell lung cancer (NSCLC) has dramatically improved outcomes. However, genomic testing uptake is variable and hampered by factors including slow turnaround time, frequently resulting in initial non-tyrosine kinase inhibitor (TKI) treatment. We investigate how this behavior affects outcomes.

Methods: This retrospective analysis of real-world, deidentified data from the Integra Connect Database included adults with stage IV NSCLC newly diagnosed from January 1, 2018, to December 31, 2020, with mutations of EGFR, ALK, ROS1, BRAF, MET, RET, ERBB2, or NTRK. Outcomes were reported as time to next treatment or death (TTNT) and overall survival (OS).

Results: Five hundred ten patients harboring AODs were identified and grouped as follows: group A (n = 379) were treated after the AOD was reported and served as the comparator. One hundred thirty-one patients treated before their AOD report were divided into group B (n = 47) who were initially started on chemotherapy and/or checkpoint inhibitor but switched to appropriate TKI within 35 days and group C (n = 84) who were also started empirically on non-TKI and did not switch within 35 days. Survival (OS) was significantly superior in group A compared with group C; TTNT was significantly superior in group A compared with groups B and C.

Conclusion: For patients harboring AODs in advanced NSCLC, initial treatment before receipt of genomic test results yields significantly inferior outcomes and should be avoided. Molecular profiling panels with rapid turnaround times are essential to optimize patient outcomes and should be standard of care.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Rushir J. Choksi

Consulting or Advisory Role: Integra Connect

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Kaplan-Meier curves for OS (A) and time to next treatment (B). Cohort definitions and corresponding data are shown in panel C. HR, hazard ratio; OS, overall survival; TKI, tyrosine kinase inhibitor; TTNT, time to next treatment.
FIG 2.
FIG 2.
Kaplan-Meier curves for OS (A) and TTNT (B) stratified by EGFR mutation status. Corresponding data are shown in panel C. Group A, patients treated after report of mutation; group B, patients treated before report of mutation, then switched to TKI within 35 days; group C, patients treated before report of mutation, then not switched to TKI within 35 days. EGFR, epidermal growth factor; HR, hazard ratio; OS, overall survival; TKI, tyrosine kinase inhibitor; TTNT, time to next treatment.
FIG A1.
FIG A1.
Integra Connect data footprint. NSCLC, non–small-cell lung cancer.
FIG A2.
FIG A2.
Patient disposition. AOD, actionable oncogenic driver; IO, immune-oncology; TKI, tyrosine kinase inhibitor.
See this image and copyright information in PMC

Comment in

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