Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib

Zhou Zhu; Nicholas C. Turner; Sherene Loi; Fabrice André; Miguel Martin; Véronique Diéras; Karen A. Gelmon; Nadia Harbeck; Cathy Zhang; Joan Q. Cao; Zhengming Yan; Dongrui R. Lu; Ping Wei; Todd L. VanArsdale; Paul A. Rejto; Xin Huang; Hope S. Rugo; Sibylle Loibl; Massimo Cristofanilli; Richard S. Finn; Yuan Liu

doi:10.1038/s41698-022-00297-1

Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib

Zhou Zhu, Nicholas C. Turner, Sherene Loi, Fabrice André, Miguel Martin, Véronique Diéras, Karen A. Gelmon, Nadia Harbeck, Cathy Zhang, Joan Q. Cao, Zhengming Yan, Dongrui R. Lu, Ping Wei, Todd L. VanArsdale, Paul A. Rejto, Xin Huang, Hope S. Rugo, Sibylle Loibl, Massimo Cristofanilli, Richard S. FinnYuan Liu

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

6 Citations (Scopus)

Résumé

While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135).

langue originale	Anglais
Numéro d'article	56
journal	npj Precision Oncology
Volume	6
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41698-022-00297-1
état	Publié - 1 déc. 2022

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10.1038/s41698-022-00297-1

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Zhu, Z., Turner, N. C., Loi, S., André, F., Martin, M., Diéras, V., Gelmon, K. A., Harbeck, N., Zhang, C., Cao, J. Q., Yan, Z., Lu, D. R., Wei, P., VanArsdale, T. L., Rejto, P. A., Huang, X., Rugo, H. S., Loibl, S., Cristofanilli, M., ... Liu, Y. (2022). Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib. npj Precision Oncology, 6(1), Article 56. https://doi.org/10.1038/s41698-022-00297-1

@article{42eb2eba23fd4bc48546ed19ae2774b8,

title = "Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib",

abstract = "While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135).",

author = "Zhou Zhu and Turner, {Nicholas C.} and Sherene Loi and Fabrice Andr{\'e} and Miguel Martin and V{\'e}ronique Di{\'e}ras and Gelmon, {Karen A.} and Nadia Harbeck and Cathy Zhang and Cao, {Joan Q.} and Zhengming Yan and Lu, {Dongrui R.} and Ping Wei and VanArsdale, {Todd L.} and Rejto, {Paul A.} and Xin Huang and Rugo, {Hope S.} and Sibylle Loibl and Massimo Cristofanilli and Finn, {Richard S.} and Yuan Liu",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "10.1038/s41698-022-00297-1",

language = "English",

volume = "6",

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Zhu, Z, Turner, NC, Loi, S, André, F, Martin, M, Diéras, V, Gelmon, KA, Harbeck, N, Zhang, C, Cao, JQ, Yan, Z, Lu, DR, Wei, P, VanArsdale, TL, Rejto, PA, Huang, X, Rugo, HS, Loibl, S, Cristofanilli, M, Finn, RS & Liu, Y 2022, 'Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib', npj Precision Oncology, VOL. 6, Numéro 1, 56. https://doi.org/10.1038/s41698-022-00297-1

TY - JOUR

T1 - Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib

AU - Zhu, Zhou

AU - Turner, Nicholas C.

AU - Loi, Sherene

AU - André, Fabrice

AU - Martin, Miguel

AU - Diéras, Véronique

AU - Gelmon, Karen A.

AU - Harbeck, Nadia

AU - Zhang, Cathy

AU - Cao, Joan Q.

AU - Yan, Zhengming

AU - Lu, Dongrui R.

AU - Wei, Ping

AU - VanArsdale, Todd L.

AU - Rejto, Paul A.

AU - Huang, Xin

AU - Rugo, Hope S.

AU - Loibl, Sibylle

AU - Cristofanilli, Massimo

AU - Finn, Richard S.

AU - Liu, Yuan

PY - 2022/12/1

Y1 - 2022/12/1

N2 - While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135).

AB - While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135).

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U2 - 10.1038/s41698-022-00297-1

DO - 10.1038/s41698-022-00297-1

M3 - Article

AN - SCOPUS:85136137422

SN - 2397-768X

VL - 6

JO - npj Precision Oncology

JF - npj Precision Oncology

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ER -