A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)

Summary

The study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

Timeline

Start

2013-02-22

Primary completion

2016-02-26

Completion

2023-11-09

Outcome

Met primary endpoint

registry MEDIAN Palbociclib Plus Letrozole: 24.8 (22.1 to NA) Months MEDIAN Placebo Plus Letrozole: 14.5 (12.9 to 17.1) Months NCT01740427 ↗

registry p <0.000001; Hazard Ratio (HR) 0.576 (95% CI 0.463 to 0.718); Stratified Log Rank NCT01740427 ↗

release “The PALOMA-2 study showed the combination of IBRANCE and letrozole extended progression-free survival (PFS)” pfizer.com ↗

release “PALOMA-2 demonstrated that the combination of IBRANCE and letrozole significantly extended progression-free survival (PFS)” pfizer.com ↗

release “for PALOMA-2, which showed a median PFS for women treated with IBRANCE plus letrozole of 24.8 months (95% CI: 22.1, NE) compared with 14.5 months” pfizer.com ↗

release “PALOMA-2 met its primary endpoint of PFS in 2016” pfizer.com ↗

Publications

• Cheang MCU, Rimawi M, Johnston S, Jacobs SA, Bliss J, Pogue-Geile K, Kilburn L, Zhu Z, Schuster EF, Xiao H, Swaim L, Deng S, Lu DR, Gauthier E, Tursi J, Slamon DJ, Rugo HS, Finn RS, Liu Y. Effect of cross-platform gene-expression, computational methods on breast cancer subtyping in PALOMA-2 and PALLET studies. NPJ Breast Cancer. 2024 Jun 29;10(1):54. doi: 10.1038/s41523-024-00658-y.
• Li H, Wu Y, Zou H, Koner S, Plichta JK, Tolaney SM, Zhang J, He YW, Wei Q, Tang L, Zhang H, Zhang B, Guo Y, Chen X, Li K, Lian L, Ma F, Luo S. Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials. EBioMedicine. 2024 Jul;105:105186. doi: 10.1016/j.ebiom.2024.105186. Epub 2024 Jun 10.
• Slamon DJ, Dieras V, Rugo HS, Harbeck N, Im SA, Gelmon KA, Lipatov ON, Walshe JM, Martin M, Chavez-MacGregor M, Bananis E, Gauthier E, Lu DR, Kim S, Finn RS. Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer. J Clin Oncol. 2024 Mar 20;42(9):994-1000. doi: 10.1200/JCO.23.00137. Epub 2024 Jan 22.
• Jhaveri K, O'Shaughnessy J, Fasching PA, Tolaney SM, Yardley DA, Sharma VK, Biswas C, Thuerigen A, Pathak P, Rugo HS. Matching-adjusted indirect comparison of PFS and OS comparing ribociclib plus letrozole versus palbociclib plus letrozole as first-line treatment of HR+/HER2- advanced breast cancer. Ther Adv Med Oncol. 2023 Dec 14;15:17588359231216095. doi: 10.1177/17588359231216095. eCollection 2023.
• Rugo HS, Im SA, Joy AA, Shparyk Y, Walshe JM, Sleckman B, Loi S, Theall KP, Kim S, Huang X, Bananis E, Mahtani R, Finn RS, Dieras V. Effect of palbociclib plus endocrine therapy on time to chemotherapy across subgroups of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Post hoc analyses from PALOMA-2 and PALOMA-3. Breast. 2022 Dec;66:324-331. doi: 10.1016/j.breast.2022.11.005. Epub 2022 Nov 15.
• Zhu Z, Turner NC, Loi S, Andre F, Martin M, Dieras 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. Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib. NPJ Precis Oncol. 2022 Aug 16;6(1):56. doi: 10.1038/s41698-022-00297-1.
• Gelmon K, Walshe JM, Mahtani R, Joy AA, Karuturi M, Neven P, Lu DR, Kim S, Schnell P, Bananis E, Schwartzberg L. Efficacy and safety of palbociclib in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2. Breast. 2021 Oct;59:321-326. doi: 10.1016/j.breast.2021.07.017. Epub 2021 Jul 28.
• Iwata H, Umeyama Y, Liu Y, Zhang Z, Schnell P, Mori Y, Fletcher O, Marshall JC, Johnson JG, Wood LS, Toi M, Finn RS, Turner NC, Bartlett CH, Cristofanilli M. Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3. Oncologist. 2021 Jul;26(7):e1143-e1155. doi: 10.1002/onco.13811. Epub 2021 Jun 7.
• Finn RS, Rugo HS, Gelmon KA, Cristofanilli M, Colleoni M, Loi S, Schnell P, Lu DR, Theall KP, Mori A, Gauthier E, Bananis E, Turner NC, Dieras V. Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up. Oncologist. 2021 May;26(5):e749-e755. doi: 10.1002/onco.13684. Epub 2021 Mar 10.
• Zheng J, Yu Y, Durairaj C, Dieras V, Finn RS, Wang DD. Impact of Dose Reduction on Efficacy: Implications of Exposure-Response Analysis of Palbociclib. Target Oncol. 2021 Jan;16(1):69-76. doi: 10.1007/s11523-020-00771-5.
• Finn RS, Cristofanilli M, Ettl J, Gelmon KA, Colleoni M, Giorgetti C, Gauthier E, Liu Y, Lu DR, Zhang Z, Bartlett CH, Slamon DJ, Turner NC, Rugo HS. Treatment effect of palbociclib plus endocrine therapy by prognostic and intrinsic subtype and biomarker analysis in patients with bone-only disease: a joint analysis of PALOMA-2 and PALOMA-3 clinical trials. Breast Cancer Res Treat. 2020 Nov;184(1):23-35. doi: 10.1007/s10549-020-05782-4. Epub 2020 Aug 11.
• Huang Bartlett C, Mardekian J, Cotter MJ, Huang X, Zhang Z, Parrinello CM, Bourla AB. Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. PLoS One. 2020 Apr 21;15(4):e0227256. doi: 10.1371/journal.pone.0227256. eCollection 2020.
• Ettl J, Im SA, Ro J, Masuda N, Colleoni M, Schnell P, Bananis E, Lu DR, Cristofanilli M, Rugo HS, Finn RS. Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies. Breast Cancer Res. 2020 Mar 12;22(1):27. doi: 10.1186/s13058-020-01263-0.
• Rugo HS, Finn RS, Gelmon K, Joy AA, Harbeck N, Castrellon A, Mukai H, Walshe JM, Mori A, Gauthier E, Lu DR, Bananis E, Martin M, Dieras V. Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2. Clin Breast Cancer. 2020 Apr;20(2):e173-e180. doi: 10.1016/j.clbc.2019.08.009. Epub 2019 Sep 5.
• Dieras V, Harbeck N, Joy AA, Gelmon K, Ettl J, Verma S, Lu DR, Gauthier E, Schnell P, Mori A, Rugo HS, Finn RS. Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Oncologist. 2019 Dec;24(12):1514-1525. doi: 10.1634/theoncologist.2019-0019. Epub 2019 Jun 19.
• Masuda N, Mukai H, Inoue K, Rai Y, Ohno S, Mori Y, Hashigaki S, Muramatsu Y, Umeyama Y, Iwata H, Toi M. Neutropenia management with palbociclib in Japanese patients with advanced breast cancer. Breast Cancer. 2019 Sep;26(5):637-650. doi: 10.1007/s12282-019-00970-7. Epub 2019 May 24.
• Im SA, Mukai H, Park IH, Masuda N, Shimizu C, Kim SB, Im YH, Ohtani S, Huang Bartlett C, Lu DR, Iyer S, Mori Y, Mori A, Gauthier E, Finn RS, Toi M. Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. J Glob Oncol. 2019 May;5:1-19. doi: 10.1200/JGO.18.00173.
• Rugo HS, Finn RS, Dieras V, Ettl J, Lipatov O, Joy AA, Harbeck N, Castrellon A, Iyer S, Lu DR, Mori A, Gauthier ER, Bartlett CH, Gelmon KA, Slamon DJ. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat. 2019 Apr;174(3):719-729. doi: 10.1007/s10549-018-05125-4. Epub 2019 Jan 10.
• Mukai H, Shimizu C, Masuda N, Ohtani S, Ohno S, Takahashi M, Yamamoto Y, Nishimura R, Sato N, Ohsumi S, Iwata H, Mori Y, Hashigaki S, Muramatsu Y, Nagasawa T, Umeyama Y, Lu DR, Toi M. Palbociclib in combination with letrozole in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: PALOMA-2 subgroup analysis of Japanese patients. Int J Clin Oncol. 2019 Mar;24(3):274-287. doi: 10.1007/s10147-018-1353-9. Epub 2018 Dec 4.
• Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N, Masuda N, Im SA, Huang X, Kim S, Sun W, Iyer S, Schnell P, Bartlett CH, Johnston S. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018 Sep;101:123-133. doi: 10.1016/j.ejca.2018.05.017. Epub 2018 Jul 25.
• Dieras V, Rugo HS, Schnell P, Gelmon K, Cristofanilli M, Loi S, Colleoni M, Lu DR, Mori A, Gauthier E, Huang Bartlett C, Slamon DJ, Turner NC, Finn RS. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. J Natl Cancer Inst. 2019 Apr 1;111(4):419-430. doi: 10.1093/jnci/djy109.
• Wedam SB, Beaver JA, Amiri-Kordestani L, Bloomquist E, Tang S, Goldberg KB, Sridhara R, Ibrahim A, Kim G, Kluetz P, McKee A, Pazdur R. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments. J Clin Oncol. 2018 Apr 20;36(12):1225-1231. doi: 10.1200/JCO.2017.74.6917. Epub 2018 Mar 9.
• Rugo HS, Dieras V, Gelmon KA, Finn RS, Slamon DJ, Martin M, Neven P, Shparyk Y, Mori A, Lu DR, Bhattacharyya H, Bartlett CHUANG, Iyer S, Johnston S, Ettl J, Harbeck N. Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial. Ann Oncol. 2018 Apr 1;29(4):888-894. doi: 10.1093/annonc/mdy012.
• Turner NC, Finn RS, Martin M, Im SA, DeMichele A, Ettl J, Dieras V, Moulder S, Lipatov O, Colleoni M, Cristofanilli M, Lu DR, Mori A, Giorgetti C, Iyer S, Bartlett CH, Gelmon KA. Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases. Ann Oncol. 2018 Mar 1;29(3):669-680. doi: 10.1093/annonc/mdx797.
• Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Dieras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. doi: 10.1056/NEJMoa1607303.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Palbociclib	Small molecule	125 mg	Oral
Comparator	Letrozole	Other / unclassified	2.5 mg	Oral

Indications