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Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer

BACKGROUND: LUX-Lung 3 showed afatinib improved progression-free survival (PFS) compared with cisplatin plus pemetrexed in patients with epidermal growth factor receptor (EGFR) mutations. In this study, chemotherapy efficacy tended to differ between patients with Leu858Arg (L858R) point mutation and...

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Autores principales: Kaneda, Toshihiko, Yoshioka, Hiroshige, Tamiya, Motohiro, Tamiya, Akihiro, Hata, Akito, Okada, Asukaka, Niwa, Takashi, Shiroyama, Takayuki, Kanazu, Masaki, Ishida, Tadashi, Katakami, Nobuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749021/
https://www.ncbi.nlm.nih.gov/pubmed/29291705
http://dx.doi.org/10.1186/s12885-017-3952-7
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author Kaneda, Toshihiko
Yoshioka, Hiroshige
Tamiya, Motohiro
Tamiya, Akihiro
Hata, Akito
Okada, Asukaka
Niwa, Takashi
Shiroyama, Takayuki
Kanazu, Masaki
Ishida, Tadashi
Katakami, Nobuyuki
author_facet Kaneda, Toshihiko
Yoshioka, Hiroshige
Tamiya, Motohiro
Tamiya, Akihiro
Hata, Akito
Okada, Asukaka
Niwa, Takashi
Shiroyama, Takayuki
Kanazu, Masaki
Ishida, Tadashi
Katakami, Nobuyuki
author_sort Kaneda, Toshihiko
collection PubMed
description BACKGROUND: LUX-Lung 3 showed afatinib improved progression-free survival (PFS) compared with cisplatin plus pemetrexed in patients with epidermal growth factor receptor (EGFR) mutations. In this study, chemotherapy efficacy tended to differ between patients with Leu858Arg (L858R) point mutation and Exon 19 deletion (Del-19); PFS in L858R patients (8.1 months) was greater than in Del-19 patients (5.6 months). We investigated whether there is any difference in efficacy of cisplatin plus pemetrexed between Del-19 and L858R. METHODS: This study is a multicenter retrospective study. We reviewed medical records of patients who had received cisplatin plus pemetrexed as first line chemotherapy. Efficacies were evaluated between EGFR mutation status: Del-19 and L858R. Wild type cases were reference arm only, and not included in any statistical analysis. RESULTS: Among 304 patients, 78 (25.7%) harbored EGFR mutations: Del-19 (36/78 patients, 46.2%); and L858R (42/78, 53.8%). Median PFS of L858R group (9.4 months, 95% confidence interval [CI]: 7.0–12.6) was significantly longer than Del-19 group (5.5 months, 95% CI, 3.6–8.6) (p = 0.049). Response rate (RR) and OS presented no significant difference between L858R and Del-19. In multivariate analysis, EGFR mutation status (L858R versus Del-19) was the only significant factor for longer PFS (Hazard ratio [HR]: 0.78, 95% CI: 0.62–0.98) (p = 0.033). CONCLUSION: Our study indicated better efficacy of cisplatin plus pemetrexed in L858R than in Del-19 patients. In EGFR-mutant NSCLC, EGFR-TKIs are undoubtedly the premier therapy. However, in second line or later settings, cisplatin plus pemetrexed regimen may confer higher efficacy for L858R patients.
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spelling pubmed-57490212018-01-05 Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer Kaneda, Toshihiko Yoshioka, Hiroshige Tamiya, Motohiro Tamiya, Akihiro Hata, Akito Okada, Asukaka Niwa, Takashi Shiroyama, Takayuki Kanazu, Masaki Ishida, Tadashi Katakami, Nobuyuki BMC Cancer Research Article BACKGROUND: LUX-Lung 3 showed afatinib improved progression-free survival (PFS) compared with cisplatin plus pemetrexed in patients with epidermal growth factor receptor (EGFR) mutations. In this study, chemotherapy efficacy tended to differ between patients with Leu858Arg (L858R) point mutation and Exon 19 deletion (Del-19); PFS in L858R patients (8.1 months) was greater than in Del-19 patients (5.6 months). We investigated whether there is any difference in efficacy of cisplatin plus pemetrexed between Del-19 and L858R. METHODS: This study is a multicenter retrospective study. We reviewed medical records of patients who had received cisplatin plus pemetrexed as first line chemotherapy. Efficacies were evaluated between EGFR mutation status: Del-19 and L858R. Wild type cases were reference arm only, and not included in any statistical analysis. RESULTS: Among 304 patients, 78 (25.7%) harbored EGFR mutations: Del-19 (36/78 patients, 46.2%); and L858R (42/78, 53.8%). Median PFS of L858R group (9.4 months, 95% confidence interval [CI]: 7.0–12.6) was significantly longer than Del-19 group (5.5 months, 95% CI, 3.6–8.6) (p = 0.049). Response rate (RR) and OS presented no significant difference between L858R and Del-19. In multivariate analysis, EGFR mutation status (L858R versus Del-19) was the only significant factor for longer PFS (Hazard ratio [HR]: 0.78, 95% CI: 0.62–0.98) (p = 0.033). CONCLUSION: Our study indicated better efficacy of cisplatin plus pemetrexed in L858R than in Del-19 patients. In EGFR-mutant NSCLC, EGFR-TKIs are undoubtedly the premier therapy. However, in second line or later settings, cisplatin plus pemetrexed regimen may confer higher efficacy for L858R patients. BioMed Central 2018-01-02 /pmc/articles/PMC5749021/ /pubmed/29291705 http://dx.doi.org/10.1186/s12885-017-3952-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kaneda, Toshihiko
Yoshioka, Hiroshige
Tamiya, Motohiro
Tamiya, Akihiro
Hata, Akito
Okada, Asukaka
Niwa, Takashi
Shiroyama, Takayuki
Kanazu, Masaki
Ishida, Tadashi
Katakami, Nobuyuki
Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
title Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
title_full Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
title_fullStr Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
title_full_unstemmed Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
title_short Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
title_sort differential efficacy of cisplatin plus pemetrexed between l858r and del-19 in advanced egfr-mutant non-squamous non-small cell lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749021/
https://www.ncbi.nlm.nih.gov/pubmed/29291705
http://dx.doi.org/10.1186/s12885-017-3952-7
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