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. 2024 Feb;166(3):461-469.
doi: 10.1007/s11060-024-04562-0. Epub 2024 Feb 7.

Converging survival trends in non-small cell lung cancer patients with and without brain metastasis receiving state-of-the-art treatment

Itamar Averbuch  1   2 , Roi Tschernichovsky  3   4   5 , Shlomit Yust-Katz  4   6 , Ofer Rotem  3   4 , Dror Limon  3   4 , Noga Kurman  3   4 , Oded Icht  3   4 , Daniel Reinhorn  3   4 , Mor Moskovitz  3   4 , Ekaterina Hanovich  3   4 , Alexandra Benouaich-Amiel  4   6 , Tali Siegal  6   7 , Alona Zer  8 , Omer Gal  3   4
Affiliations

Converging survival trends in non-small cell lung cancer patients with and without brain metastasis receiving state-of-the-art treatment

Itamar Averbuch et al. J Neurooncol. 2024 Feb.

Abstract

Introduction: Historically, patients with brain metastasis (BM) have been excluded from clinical trials investigating treatments for non-small cell lung cancer (NSCLC) due to their unfavorable prognosis. Advanced treatments have increased survival prospects for NSCLC patients with BM. This study evaluated the life expectancy of NSCLC patients with and without BM in the context of contemporary treatments.

Methods: Outcome data were collected for patients with advanced NSCLC attending a tertiary medical center between 2015 and 2020. Patients were stratified according to BM status and compared for overall survival (OS) using log-rank and Cox regression analyses.

Results: The cohort included 360 patients with NSCLC of whom 134 (37.2%) had BM. Most (95%) of cases of BM developed within the first two years: 63% at diagnosis, 18% during the first year, 14% during the second year. There was no significant difference in OS between patients without BM and those with BM (median 23.7 vs. 22.3 months, HR = 0.97, p = 0.82); patients with BM and a targetable or non-targetable mutation (40.2 vs. 31.4 months, HR = 0.93, p = 0.84, and 20.7 vs. 19.87 months, HR = 0.95, p = 0.75, respectively); and patients with symptomatic BM (23.7 vs. 19.8 months, HR = 0.95, p = 0.78). Treatment for BM (95% of patients) consisted of stereotactic radiosurgery or tyrosine kinase inhibitors, with corresponding intracranial control rates of 90% and 86%.

Conclusion: The results imply that the presence of BM has no impact on the prognosis of NSCLC. The practice of excluding NSCLC patients with BM from clinical trials warrants reconsideration.

Keywords: Brain metastasis; Non small cell lung cancer; Prognosis.

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Conflict of interest statement

The authors declare no competing interests.

Itamar Averbuch reports receiving personal fees from Merck Serono outside the submitted work. Alona Zer reports receiving consulting fees from Nixio; payment/honoraria from MSD, Takeda, and AstraZeneca; support for meetings/travel from MSD; participation on Data Safety Monitoring or Advisory Boards for XAIR and AstraZeneca; stock/stock options in Nixio, outside the submitted work. Mor Moskovitz reports receiving grants/contracts from Rabin, Southwestern University, and AstraZeneca; consulting fees from MSD, AstraZeneca, Takeda, Pfizer, Roche, Novartis; payment/honoraria from MSD, AstraZeneca, Takeda, Pfizer, Roche, BMS, JNJ; support for meetings/travel from Pfizer, Roche, outside the submitted work. Oded Icht reports receiving consulting fees from Brainlab; payment/honoraria from AstraZeneca and Roche, outside the submitted work. Ofer Rotem reports receiving consulting fees from AstraZeneca, Boehringer Ingelheim, BMS, Edocate, MSD, Novartis, Nucleai, Pfizer, Rhenium, Roche, Takeda, Teva; payment/honoraria and support for meetings/travel from AstraZeneca, Boehringer Ingelheim, BMS, MSD, Novartis, Pfizer, Rhenium, Roche, Takeda, Teva, outside the submitted work. Daniel Reinhorn reports receiving payment/honoraria from BMS and AstraZeneca, outside the submitted work. Shlomit Yust-Katz reports receiving grants/contracts from MSK; consulting fees from Pfizer; payment/honoraria from Pfizer, Teva, Eli-Lilly, and Abbvie; support for meetings/travel from Novocure; participation on Data Safety Monitoring or Advisory Boards from Pfizer, outside the submitted work. Roi Tschernichovsky, Dror Limon, Noga Kurman, Ekaterina Hanovich, Alexandra Benouaich-Amiel, Tali Siegal, and Omer Gal report no conflict of interest.

Figures

Fig. 1
Fig. 1
Chart flow
Fig. 2
Fig. 2
The ratio of patients with brain metastases among the overall surviving patients at yearly intervals following the diagnosis of NSCLC
Fig. 3
Fig. 3
The yearly rate of patients developing brain metastases out of the entire group of patients with BM
Fig. 4
Fig. 4
Overall survival by BM status. (A) Patients with BM at diagnosis of NSCLC compared to patients without BM. (B) Patients with BM at any time during the disease course compared to patients without BM. (C) Patients with symptomatic BM compared to patients without BM. (D) Patients with symptomatic BM compared to patients with non-symptomatic BM
Fig. 5
Fig. 5
Overall survival stratified by brain metastasis status, performance status, and TKIs status. (A) Comparison of TKI-Treated or non-TKI-Treated patients with and without BM. (B) Comparison of patients with Good/Poor ECOG performance status with and without BM
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