Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial
PurposeJUNIPER, a randomized, phase III trial of patients with stage IV non–small cell lung cancer and a detectable Kristen rat sarcoma (KRAS) mutation in codons 12 or 13 whose condition progressed after platinum-based chemotherapy and up to 1 additional therapy (could include immune checkpoint inhi...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1461530/full |
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| author | Jiangang Liu Hong Wang Amit Aggarwal Maria Jesus Ortiz-Ruiz Elisabet Zapatero-Solana Maria Jose Lallena Sandra Peregrina Gloria Martinez del Hoyo Susana Velasco Philip J. Ebert Xueqian Gong Anwar M. Hossain Shawn T. Estrem |
| author_facet | Jiangang Liu Hong Wang Amit Aggarwal Maria Jesus Ortiz-Ruiz Elisabet Zapatero-Solana Maria Jose Lallena Sandra Peregrina Gloria Martinez del Hoyo Susana Velasco Philip J. Ebert Xueqian Gong Anwar M. Hossain Shawn T. Estrem |
| author_sort | Jiangang Liu |
| collection | DOAJ |
| description | PurposeJUNIPER, a randomized, phase III trial of patients with stage IV non–small cell lung cancer and a detectable Kristen rat sarcoma (KRAS) mutation in codons 12 or 13 whose condition progressed after platinum-based chemotherapy and up to 1 additional therapy (could include immune checkpoint inhibitors), reported prolonged progression-free survival (PFS) but not overall survival (OS) among patients who were receiving abemaciclib versus those who were receiving erlotinib. To establish whether certain patient subgroups received an OS benefit from the addition of abemaciclib to best supportive care, JUNIPER patients were retrospectively evaluated for KRAS co-mutation gene expression subtype, and abemaciclib efficacy was assessed for each patient subgroup.Materials and methodsOf the 453 patients enrolled in the JUNIPER trial, tumor specimens for biomarker analysis were available for 148 (abemaciclib arm, n=79; erlotinib arm, n=69). Samples were profiled for gene expression and classified into 3 previously identified expression subtypes (KL, KP, and K). Tumor response, OS, and PFS were assessed within each subtype.ResultsRetrospective analyses of expression subtypes revealed an OS advantage for patients with KL subtype tumors who were receiving abemaciclib versus those with the KL subtype who were receiving erlotinib (median, 13.05 vs 5.65 months; hazard ratio, 0.25; 95% confidence interval, 0.09–0.73; P=.011). KL and KP expression subtype groups derived a PFS benefit from abemaciclib versus erlotinib (KL median, 6.64 vs 2.1 months; hazard ratio, 0.12; 95% confidence interval, 0.03–0.41; P=.001, and KP median, 5.52 vs 2.24 months; hazard ratio, 0.44; 95% confidence interval, 0.23–0.84; P=.013). Patients with K subtype tumors received no OS or PFS benefit from abemaciclib treatment.ConclusionsPatients with KL expression subtype tumors may derive better OS and PFS from abemaciclib versus erlotinib in KRAS-mutated non–small cell lung cancer. These results should be further validated in an independent dataset. |
| format | Article |
| id | doaj-art-1a483ccad012425da434dd0e8a08dda7 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-1a483ccad012425da434dd0e8a08dda72025-08-20T03:41:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-03-011510.3389/fonc.2025.14615301461530Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER TrialJiangang Liu0Hong Wang1Amit Aggarwal2Maria Jesus Ortiz-Ruiz3Elisabet Zapatero-Solana4Maria Jose Lallena5Sandra Peregrina6Gloria Martinez del Hoyo7Susana Velasco8Philip J. Ebert9Xueqian Gong10Anwar M. Hossain11Shawn T. Estrem12Eli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Madrid, SpainCell Signaling and Immunometabolism Laboratory, Centro de Investigaciones Oncológicas, Madrid, SpainCell Signaling and Immunometabolism Laboratory, Centro de Investigaciones Oncológicas, Madrid, SpainCell Signaling and Immunometabolism Laboratory, Centro de Investigaciones Oncológicas, Madrid, SpainEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesEli Lilly and Company, Indianapolis, IN, United StatesPurposeJUNIPER, a randomized, phase III trial of patients with stage IV non–small cell lung cancer and a detectable Kristen rat sarcoma (KRAS) mutation in codons 12 or 13 whose condition progressed after platinum-based chemotherapy and up to 1 additional therapy (could include immune checkpoint inhibitors), reported prolonged progression-free survival (PFS) but not overall survival (OS) among patients who were receiving abemaciclib versus those who were receiving erlotinib. To establish whether certain patient subgroups received an OS benefit from the addition of abemaciclib to best supportive care, JUNIPER patients were retrospectively evaluated for KRAS co-mutation gene expression subtype, and abemaciclib efficacy was assessed for each patient subgroup.Materials and methodsOf the 453 patients enrolled in the JUNIPER trial, tumor specimens for biomarker analysis were available for 148 (abemaciclib arm, n=79; erlotinib arm, n=69). Samples were profiled for gene expression and classified into 3 previously identified expression subtypes (KL, KP, and K). Tumor response, OS, and PFS were assessed within each subtype.ResultsRetrospective analyses of expression subtypes revealed an OS advantage for patients with KL subtype tumors who were receiving abemaciclib versus those with the KL subtype who were receiving erlotinib (median, 13.05 vs 5.65 months; hazard ratio, 0.25; 95% confidence interval, 0.09–0.73; P=.011). KL and KP expression subtype groups derived a PFS benefit from abemaciclib versus erlotinib (KL median, 6.64 vs 2.1 months; hazard ratio, 0.12; 95% confidence interval, 0.03–0.41; P=.001, and KP median, 5.52 vs 2.24 months; hazard ratio, 0.44; 95% confidence interval, 0.23–0.84; P=.013). Patients with K subtype tumors received no OS or PFS benefit from abemaciclib treatment.ConclusionsPatients with KL expression subtype tumors may derive better OS and PFS from abemaciclib versus erlotinib in KRAS-mutated non–small cell lung cancer. These results should be further validated in an independent dataset.https://www.frontiersin.org/articles/10.3389/fonc.2025.1461530/fullbiomarkersCDK4CDK6KRASnon-small cell lung cancer clinical trial registration: NCT02152631 |
| spellingShingle | Jiangang Liu Hong Wang Amit Aggarwal Maria Jesus Ortiz-Ruiz Elisabet Zapatero-Solana Maria Jose Lallena Sandra Peregrina Gloria Martinez del Hoyo Susana Velasco Philip J. Ebert Xueqian Gong Anwar M. Hossain Shawn T. Estrem Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial Frontiers in Oncology biomarkers CDK4 CDK6 KRAS non-small cell lung cancer clinical trial registration: NCT02152631 |
| title | Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial |
| title_full | Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial |
| title_fullStr | Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial |
| title_full_unstemmed | Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial |
| title_short | Survival benefit from abemaciclib in non–small cell lung cancer by Kirsten rat sarcoma–mutation gene expression subtype: retrospective analysis from the JUNIPER Trial |
| title_sort | survival benefit from abemaciclib in non small cell lung cancer by kirsten rat sarcoma mutation gene expression subtype retrospective analysis from the juniper trial |
| topic | biomarkers CDK4 CDK6 KRAS non-small cell lung cancer clinical trial registration: NCT02152631 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1461530/full |
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