KOL Pulse Trial Profile - PADMA | Ibrance (palbociclib) in 1L HR+/HER2- mBC

Q: What is the PADMA trial?

PADMA (NCT03355157) is a randomized, open-label, multicenter Phase IV trial from the German Breast Group (GBG) comparing first-line palbociclib (Ibrance) plus endocrine therapy against chemotherapy in patients with HR-positive, HER2-negative metastatic breast cancer who had an indication for chemotherapy. It provides prospective, randomized head-to-head data for these two first-line strategies.

Q: What did PADMA show?

Palbociclib plus endocrine therapy significantly improved median progression-free survival to 18.7 versus 7.8 months with chemotherapy (hazard ratio 0.45; 95% CI 0.29-0.70; p<0.001), with time to treatment failure of 17.2 versus 6.1 months. Overall survival showed a numerical trend favoring palbociclib plus endocrine therapy (46.1 versus 36.8 months) that was not statistically significant.

Q: Is palbociclib (Ibrance) FDA approved?

Yes. Palbociclib (Ibrance, Pfizer) is FDA-approved in combination with endocrine therapy for HR-positive, HER2-negative advanced or metastatic breast cancer. PADMA itself is an investigator-initiated randomized comparison of palbociclib plus endocrine therapy versus chemotherapy and is not a separate FDA registration trial.

Q: How did safety compare between palbociclib plus endocrine therapy and chemotherapy?

Hematologic toxicity was more common with palbociclib plus endocrine therapy (any-grade hematologic treatment-related adverse events 96.8% versus 58.6%; grade 3-4 54.8% versus 6.9%), while non-hematologic adverse events were comparable between the arms. The palbociclib hematologic events, chiefly neutropenia, are generally manageable with monitoring and dose adjustment.

Q: Why is PADMA clinically important?

PADMA provides prospective, randomized evidence that CDK4/6 inhibitor-based endocrine therapy is superior in progression-free survival to chemotherapy as first-line treatment in high-risk HR-positive, HER2-negative metastatic breast cancer patients who otherwise had a chemotherapy indication, reinforcing guideline preference for endocrine therapy plus a CDK4/6 inhibitor.

At a Glance

PADMA Key Takeaways

Design - Randomized Phase IV German Breast Group trial: first-line palbociclib (Ibrance) + endocrine therapy vs chemotherapy, HR+/HER2- metastatic breast cancer with a chemotherapy indication (NCT03355157).

PFS - Median 18.7 vs 7.8 months, HR 0.45 (95% CI 0.29-0.70; p<0.001) favoring palbociclib + endocrine therapy; time to treatment failure 17.2 vs 6.1 months (HR 0.46).

OS - Numerical trend favoring palbociclib + endocrine therapy but not statistically significant: median 46.1 vs 36.8 months (HR 0.81; 95% CI 0.46-1.43; p=0.4630).

Safety - More hematologic toxicity with palbociclib (any-grade hematologic TRAEs 96.8% vs 58.6%; grade 3-4 54.8% vs 6.9%); non-hematologic AEs comparable.

Regulatory - Palbociclib (Ibrance) is FDA-approved with endocrine therapy in HR+/HER2- advanced/metastatic breast cancer; PADMA is an investigator-initiated comparative trial, not a new registration.

Sponsor / drug - German Breast Group (GBG); palbociclib (Ibrance) + endocrine therapy.

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.

Influence Leaders

Top KOLs Discussing PADMA

Sara Tolaney

@stolaney1

11.9K impressions

Oncology Brothers

@OncBrothers

6.7K impressions

Hope Rugo

@hoperugo

4.1K impressions

Erika Hamilton, MD

@ErikaHamilton9

2.6K impressions

Elisa Agostinetto

@ElisaAgostinett

2.4K impressions

Harold J. Burstein, MD, PhD, FASCO

@DrHBurstein

2.0K impressions

Conference Presentations

PADMA Key Slides & Visuals

Official trial slides and relevant visuals shared by KOLs at SABCS 2024 (#SABCS24). Click any image to expand.

Sara Tolaney @stolaney1

PADMA Data

11.9K impressions · 112 likes · Dec 11, 2024

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[Slide 1] Unmute proadcast SAN ANTONIO ORDAST CANCER SYMPOSIUM las America - Cames - Income SAN ANTONIO BREAST CANCER Primary Endpoint VIMPOSUM 1 AAC - 100% fulgroup . I Prote 3 @ pustemis DOBIN 90% I EM I NOTE --- 10% 18 0.00 60% | M BOB. - I H one 40% - 30% OR - 30% E H 10% - E : ! 8 A : # 6 12 R 16 - H 2 " I ! 5 - - CT bened YP H. M 6 5 1 r 1 1 5 M or a 11 41 R * If 11 # * 1 H 1 - I ITI, months n ON 14 Patient + ET CT as 1. $5 TTF events, N (%) 45 (73.5) 55 (93.2) Median TTF months 17.2 6.1 HR 0.48 95% CI (6.31-0.89) p-8.001 (og-cank) I I 686 Median follow-up of 36.0 (range 0-74.4) months PADMA The in - - preparity of the Contain - - - to premission = reprind - -

Hope Rugo @hoperugo

PADMA Data

4.1K impressions · 54 likes · Dec 11, 2024

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[Slide 1] BRINGING THE WORLD OF EP TOGETHER SAN ANTONIO BREAST CANCER SYMPOSIUM See Antonio Dreamt Concer Dymposismit, December 90-53, 2024 SAN ANTONIO BREAST CANCER Primary Endpoint SYMPOSIUM These AACR 1 100% Subgroup N MaiardRaSo p-Water Test for patients reteraction 90% Overall 130 Treatment failure free Rate (%) <.001 80% Response IT 0.630 70% required 18 0.342 60% VITABLE 2 0.001 50% Symptoms 0.572 symptomatic VI 3271 290, - DDE 40% inymplormatic to $ DA 7511 0.005 30% Uver metantines 0.144 no 12 Issued 271, 0.007 20% yes 50 3551 138 XXI 0.005 10% Number of system 0.230 1/2 2% ase <001 0% X 45 642 543, 1.21) 0.170 0 6 12 18 24 30 36 42 48 Metantion If primary diagnosis 0.799 MD 7% 4571 XMI 0.001 CT based 59 11 10 6 5 3 2 1 1 MO " 481 57M 0.042 Prior - early N 0.334 no (4) 347,1.054 0.073 61 41 30 26 21 13 8 6 2 Yes 54 <001 - - 0544 TTP. months ER+FER 25 0.1% 54 4171 250, <001 Palbociclib + ET CT 1.5 1 1.5 TTF events, N (%) 45(73.8) 55 (93.2) HK Median TTF months 17.2 6.1 tonges TIF - FT larger IDF will 11 HR 0.46 95% CI (0.31-0.69) p<0.001 (log-rank) GBG Median follow-up of 36.8 (range 0-74.4) months ****** PADMA This presentation is The property of The Contact then . for permission to represt - SHOUP DECEMBER 10- 2024 SANANTONIO --- [Slide 2] BRINGING THE WORLD OF EP TOGETHER SAN ANTONIO BREAST CANCER SYMPOSIUM Sen Antonio Drest Concer December 90-53, 2024 SAN ANTONIO BREAST CANCER Secondary Endpoints SYMPOSIUM - AACR THE 100% 100% 90% 50% Progression-Free Free Survival Rate INI 80% 80% 70% 60% Overall Survival Rate (%) 70% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% 0 6 12 18 24 30 36 42 48 0 6 12 18 24 30 36 42 48 CT based 59 35 13 7 6 3 2 1 1 CT based 59 52 42 R 25 16 15 7 3 Palbocicib+ET 61 43 32 27 23 15 E 6 3 Palbocidib+ET 61 52 42 37 33 25 19 15 9 PFS, months Overall Survival months Palbociclib ET CT Palbociclib ET CT PFS events, N (%) 40 (65.6) 50 (84.7) OS events, N (%) 25 (41.0) 24 (40.7) Median PFS months 18.7 7.8 Median OS months 46.1 36.8 HR 0.45 95% CI (0.29-0.70). p<0.001 (log-rank) Proportional hazard cannot be assumed GBG ****** PADMA This presentation is The property of The a Contact Ben if - for permission to reprist - - GROUP DECEMBER 10- 14, 2024 SANANTONIO --- [Slide 3] BRINGING THE WORLD OF EP TOGETHER SAN ANTONIO BREAST CANCER SYMPOSIUM See Antonio Dreamt Concer Symposismi, December 90-53. 2024 SAN ANTONIO BREAST CANCER Conclusions SYMPOSIUM - AACR - - The PADMA trial in high-risk HR+/HER2- mBC met its primary endpoint and shows a statistically significant and clinically meaningful improvement in Time To Treatment Failure and PFS for palbociclib + ET over mono-CT (+ ET maintenance) as first-line therapy Median TTF 17.2 VS 6.1 months : HR 0.46, 95% CI (0.31-0.69). p<0.001 Median PFS 18.7 VS 7.8 months; HR 0.45, 95% CI (0.29-0.70). p<0.001 After a median follow-up of 36.8 months there was a numerical trend for an improved OS for palbociclib + ET 46.1 VS 36.8 months No new safety signals were observed These results support existing international guidelines advocating the use of ET + CDK4/6i as standard first-line treatment of patients with HR+/HER2- mBC. GBG PADMA This presentation is the property of THE a Contact them - for to reprint - - GROUP DECEMBER 10 2024 SANANTONIO

Erika Hamilton, MD @ErikaHamilton9

PADMA Data

2.6K impressions · 33 likes · Dec 11, 2024

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[Slide 1] San Antonio Breast Cancer Symposium®, December 10-13, 2024 PADMA Study Design SAN ANTONIO BREAST CANCER SYMPOSIUM® UT Health AACR - - - Patient Population Map - Cost N=150 HR-positive/HER2-negative Female or male Arm A Endocrine therapy (ET) + palbociclib Indication for mono-chemotherapy No prior treatment for metastatic/relapsed disease 1:1 R No asymptomatic bone-only, oligo- metastatic disease No uncontrolled/untreated CNS Chemotherapy (CT) of Arm B physician's choice ± ET metastases maintenance therapy Live-expectancy >6 months Stratification: ET with palbociclib: Al or fulvestrant ± GnRHa - Endocrine resistant VS endocrine sensitive ET maintenance: tamoxifen, Al or fulvestrant ± GnRHa - Symptomatic vs asymptomatic metastatic disease CT: paclitaxel, capecitabine, epirubicin, or vinorelbine GBG GERMAN BREAST GROUP PADMA This presentation is the intellectual property of the author/presenter. Contact them at publications@obq. de for permission to reprint and/or distribute. --- [Slide 2] San Antonio Breast Cancer Symposium®, December 10-13, 2024 SAN ANTONIO BREAST CANCER SYMPOSIUM Baseline Characteristics UT Health AACR - Mays - CT-based Overall Palbociclib+ET N=61 N=59 N=120 Median age in years (range) 63 (42.0-85.0) 62 (31.0-80.0) 62 (31.0-85.0) Postmenopausal status 54 (88.5%) 52 (88.1%) 106 (88.3%) Liver metastases 28 (45.9%) 22 (37.3%) 50 (41.7%) Endocrine resistant* 17 (27.9%) 21 (35.6%) 38 (31.7%) Metastasis at initial diagnosis 20 (33.3%) 24 (40.7%) 44 (37.0%) Prior (neo)adjuvant CT 29 (47.5%) 25 (42.4%) 54 (45.0%) HER2-low (IHC 1-2)** 41 (73.2%) 30 (58.8%) 71 (66.4%) Pathogenic variants (tissue)*** PIK3CA 11 (18.0%) 16 (27.1%) 27 (22.5%) BRCA1/2 3 (4.9%) 4 (6.8%) 7 (5.8%) ESR1 1 (1.6%) 1 (1.7%) 2 (1.7%) GBG . According to clean data; endocrine resistant = relapse on or within 12 months of end of adjuvant ET " From metastasis (N=47), otherwise if available from initial diagnosis (N=24) GERMAN *** Tested in 81 patients. BREAST GROUP PADMA This presentation is the intellectual property of the author/presenter. Contact them at publications maha de for permission to reprint and/or distribute. --- [Slide 3] San Antonio Breast Cancer Symposium®, December 10-13, 2024 SAN ANTONIO BREAST CANCER Primary Endpoint SYMPOSIUM UT Health AACR - - - - Mays Case Cent 100% Hazard Ratio p-Value Test for Subgroup N (95% CI) Interaction 90% patients <,001 Treatment-failure-free Rate (%) 80% Overall 120 461 (.306, 695) 0.430 70% Response to ET Hormone resistant 38 .590 (.282, 1.24) 0.162 60% Hormone sensitive 82 430 (.259,.713) 0.001 0.572 50% Symptoms symptomatic 527 (.290, 959) 0.036 54 40% asymptomatic 66 .399 (.218,.731) 0.003 0.144 30% Liver metastases no 70 469 (.271, .810) 0.007 20% yes 50 353 (.178, .700) 0.003 0.230 10% Number of systems with metastases 0% 1/2 75 359 (.207, 624) <.001 >2 45 642 (.340, 1.21) 0.170 0.799 0 6 12 18 24 30 36 42 48 Metastasis at primary diagnosis M0 76 .417 (.247, 704) 0.001 CT based 59 31 10 5 3 1 1 M1 44 481 (.238, 973) 0.042 6 2 Prior chemotherapy in early BC 0.334 Palbociclib+ET 61 no 66 .603 (.347, 1.05) 0.073 41 30 26 21 13 8 6 2 yes 54 .293 (.154, 555) <.001 HR-status in ER positive 0.544 TTF, months ER+ PgR- 25 .553 (.227, 1.35) 0.192 ER+ PgR+ 94 412 (.256, 662) <.001 Palbociclib + ET CT 0.5 1 1.5 TTF events, N (%) 45 (73.8) 55 (93.2) HR Median TTF months 17.2 6.1 Longer TTF with Palbociclib + ET Longer TTF with CT HR 0.46: 95% CI (0.31-0.69), p<0.001 (log-rank) GBG Median follow-up of 36.8 (range 0-74.4) months GERMAN BREAST PADMA GROUP This presentation is the intellectual property of the author/presenter. Contact them at publications@gbq de for permission to reprint and/or distribute. --- [Slide 4] San Antonio Breast Cancer Symposium®, December 10-13, 2024 SAN ANTONIO BREAST CANCER Secondary Endpoints SYMPOSIUM UT Health AACR - - - - Mays Came - 100% 100% 90% Progression-Free Survival Rate (%) 90% 80% 80% 70% 60% 50% Overall Survival Rate (%) 70% 60% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% 0 6 12 18 24 30 36 42 48 0 6 12 18 24 30 36 42 48 CT based 59 35 13 7 6 3 2 1 1 CT based 59 52 42 29 25 16 15 7 3 Palbociclib+ET 61 43 32 27 23 15 8 6 3 Palbociclib+ET 61 52 42 37 33 25 19 15 9 PFS, months Overall Survival, months Palbociclib + ET CT Palbociclib + ET CT PFS events, N (%) 40 (65.6) 50 (84.7) OS events, N (%) 25 (41.0) 24 (40.7) Median PFS months 18.7 7.8 Median OS months 46.1 36.8 HR 0.45 95% CI (0.29-0.70), p<0.001 (log-rank) Proportional hazard cannot be assumed GBG GERMAN BREAST PADMA GROUP This presentation is the intellectual property of the author/presenter. Contact them at publications@abq. de for permission to reprint and/or distribute.

Elisa Agostinetto @ElisaAgostinett

PADMA Data

2.4K impressions · 16 likes · Dec 11, 2024

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[Slide 1] San Antonio Breast Cancer Symposiume, December 10-13, 2024 SAN ANTONIO BREAST CANCER PADMA Study Design SYMPOSIUM UT Health AACR I I I Patient Population N=150 HR-positive/HER2-negative Arm A Endocrine therapy (ET) + Female or male palbociclib Indication for mono-chemotherapy No prior treatment for metastatic/relapsed disease 1:1 R No asymptomatic bone-only, oligo- metastatic disease Chemotherapy (CT) of No uncontrolled/untreated CNS Arm B physician's choice ± ET metastases maintenance therapy Live-expectancy >6 months Stratification: ET with palbociclib: Al or fulvestrant ± GnRHa - Endocrine resistant VS endocrine sensitive ET maintenance: tamoxifen, Al or fulvestrant ± GnRHa - Symptomatic VS asymptomatic metastatic disease CT: paclitaxel, capecitabine, epirubicin, or vinorelbine GBG GERMAN PADMA BREAST This presentation is the Intellectual property of the author/presenter. Contact them at publications@obq. de for permission to reprint and/or distribute. GROUP --- [Slide 2] San Antonio Breast Cancer Symposiumic, December 10-13, 2024 SAN ANTONIO Primary Endpoint BREAST CANCER SYMPOSIUM Health AAGR 100% 90% Subgroup N Hazard Ratio p-Value Test for patients (95%CI) Interaction Treatment-failure-free Rate (%) 80% Overall 120 461 (.306, 695) <.001 70% Response to ET 0.430 60% Hormone resistant 38 590 (282,1.24) 0.162 50% Hormone sensitive 82 430 (.259, 713) 0.001 Symptoms 0.572 40% symptomatic 54 527 (.290, 959) 0.036 30% asymptomatic 66 399 (218,731) 0.003 Liver metastases 0.144 20% no 70 469 (271,810) 0.007 10% yes 50 353 (.178,.700) 0.003 Number of systems with metastases 0.230 0% 1/2 75 359 (.207, 624) <.001 0 >2 6 45 12 18 642 (340, 1.21) 0.170 24 30 36 42 48 Metastasis at primary diagnosis 0.799 M0 CT based 76 59 417 (.247, 704) 0.001 31 10 6 5 3 2 1 1 M1 44 481 (.238, 973) 0.042 Prior chemotherapy in early BC 0.334 Palbociclib+ET 61 41 30 26 21 13 no 8 6 66 2 603 (347, 1.05) 0.073 yes 54 293 (.154, 555) <.001 HR-status in ER positive 0.544 TTF, months ER+ PgR. 25 553 (.227,1.35) 0.192 ER+ PgR+ 94 412 (.256, .662) <.001 Palbociclib + ET CT TTF events, N (%) 0.5 1 1.5 45 (73.8) 55 (93.2) Median TTF months 17.2 6.1 HR HR 0.46: 95% CI (0.31-0.69), p<0.001 (log-rank) Longer TTF with Palbocidib . ET Longer TTF with CT GBG PADMA Median follow-up of 36.8 (range 0-74.4) months GERMAN BREAST This presentation is the intellectual property of the author/presenter. Contact them at publications@abq de for permission to reprint and/or distribute. GROUP --- [Slide 3] San Antonio Breast Cancer Symposiume, December 10-13, 2024 SAN ANTONIO Secondary Endpoints BREAST CANCER SYMPOSIUM THalth AAGR for | 100% 90% 100% Progression-Free Survival Rate (%) 80% 90% 70% 80% 60% Overall Survival Rate (%) 70% 50% 60% 40% 50% 30% 40% 20% 30% 10% 20% 0% 10% 0% 0 6 12 18 24 30 36 42 48 0 6 12 18 24 30 36 42 48 CT based 59 35 13 7 6 3 2 1 1 CT based 59 52 42 29 25 16 15 7 3 Palbociclib+ET 61 43 32 27 23 15 8 6 3 Palbociclib+ET 61 52 42 37 33 25 19 15 9 PFS, months Overall Survival, months Palbociclib + ET CT Palbociclib + ET CT PFS events, N (%) 40 (65.6) 50 (84.7) OS events, N (%) 25 (41.0) 24 (40.7) Median PFS months 18.7 7.8 Median OS months 46.1 36.8 HR 0.45 95% CI (0.29-0.70), p<0.001 (log-rank) Proportional hazard cannot be assumed GBG GERMAN PADMA BREAST This presentation is the Intellectual property of the author/presenter Contact them at publications Daba de for permission to reprint and/or distribute. GROUP

Harold J. Burstein, MD, PhD, FASCO @DrHBurstein

PADMA Data

2.0K impressions · 31 likes · Dec 11, 2024

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[Slide 1] Sam Antonio Breast Cancer December 2024 SAN ANTONIO Primary Endpoint BREAST CANCER SYMPOSIUM UT Health AACR - 100% Subgroup N Hazard Ratio Value Test for 90% patients (95% (I) Interaction Treatment-failure-free Rate (%) 80% Overall 120 461 (.306, 695) <.001 70% Response to ET 0.430 Hormone resistant 38 590 60% 282,1.24) 0.162 Hormone sensitive 82 430 259,713) 0.001 50% Symptoms 0.572 symptomatic 54 40% 527 290,959) 0.036 asymptomatic 66 399 218,731) 0.003 30% Liver metastases 0.144 no 20% 70 469 (271,810) 0.007 yes 50 353 178,700) 0.003 10% Number of systems with metastases 0.230 0% 1/2 75 359 207,624) <001 >2 45 642 340,1.21) 0.170 0 6 12 18 24 30 36 42 48 Metastasis at primary diagnosis 0.799 MO 76 417 247,704) 0.001 CT based 59 31 10 6 5 3 2 1 1 M1 44 481 238,973) 0.042 Prior chemotherapy in early BC 0.334 Palbociclib+ET 61 no 66 603 41 30 26 347,1.05) 0.073 21 13 8 6 2 yes 54 293 154,555) <.001 HR-status in ER positive 0.544 TTF, months ER+ PgR. 25 553 (227,1.35) 0.192 ER+ PgR+ 94 412 256,.662) <001 Palbociclib + ET CT 0.5 1 1.5 TTF events, N (%) 45 (73.8) 55 (93.2) HR Median TTF months 17.2 6.1 Longer TTF with Palbocidib . ET Longer TTF with CT HR 0.46: 95% CI (0.31-0.69), p<0.001 (log-rank) GBG Median follow-up of 36.8 (range 0-74.4) months GERMAN BREAST PADMA GROUP This presentation is the Intellectual property of the author/presenter. Contact them at publications@gbq.de for permission to reprint and/or distribute.

Dr Amol Akhade @SuyogCancer

PADMA Data

1.7K impressions · 20 likes · Dec 11, 2024

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[Slide 1] SAN ANTONIO BREAST CANCER SYMPOSIUM San Antenie Brent Camout Symposiummil, December 10-53,2024 SAN ANTONIO BREAST CANCER Conclusions SYMPOSIUM UT Health AACH The PADMA trial in high-risk HR+/HER2- mBC met its primary endpoint and shows a statistically significant and clinically meaningful improvement in Time To Treatment Failure and PFS for palbociclib + ET over mono-CT (+ ET maintenance) as first-line therapy Median TTF 17.2 vs 6.1 months : HR 0.46. 95% CI (0.31-0.69). p<0.001 Median PFS 18.7 vs 7.8 months; HR 0.45, 95% CI (0.29-0.70), p<0.001 After a median follow-up of 36.8 months there was a numerical trend for an improved os for palbociclib + ET 46.1 vs 36.8 months No new safety signals were observed These results support existing international guidelines advocating the use of ET + CDK4/6i as standard first-line treatment of patients with HR+/HER2- mBC. GBG PADMA This presentation H the property of The authorized Contact them at for pervession to represe added (institute 1.4 --- [Slide 2] SAN ANTONIO BREAST CANCER SYMPOSIUM San Antenie Breant Cancer Symposium December 10-13,2004 SAN ANTONIO BREAST CANCER Primary Endpoint SYMPOSIUM UT Health AACH Subgroup N 100% Satard Peter problem Test for patiento (96% C) interaction 90% Overall 130 4611.106, east <.001 50% Response to ET 0.400 70% resident is 5901.202.1.24 0.152 60% Wormen 82 4301.159.3138 0.001 Symptoms 0.572 50% symptomatic St DDE 40% 14 3991.238.3318 0.005 30% Over 0.144 no 0.007 20% yes 50 3551.178,3000 0.005 10% Number of services with recturings 0.233 1/2 IS <001 0% w 45 6421.540.1.21 0.170 0 6 12 18 24 30 36 42 as Metarstank of primury 0.799 MO is 4571.242.3041 0.001 CT based 59 31 10 a 5 3 2 1 1 MI 4.0 4811.238.575 DIDE Prior early BC 0.334 is 6031.247.1054 0.023 61 41 30 26 21 13 8 6 2 yes 54 4.001 HM 0.544 TTF. months 35 0.190 of < 001 Palbociclib + ET CT #.5 1 1.5 TTF events, N (%) 45 (73.8) 55 (93.2) HR Median TTF months 17.2 6.1 Ineger with HR 0.46 95% CI (0.31-0.69) p<0.001 (log-rank) GBG Median follow-up of 36.8 (range 0-74.4) months PADMA This presentation H The property of The Contact them M (************ Tar estimate --- [Slide 3] BRINGING THE WORLD OF EP TOGETHE 8 SAN ANTONIO BREAST CANCER SYMPOSIUM San Anterio Breat Concern Symposium December 10-53. 2024 SAN ANTONIO AST CANCER Secondary Endpoints SYMPOSIUM UT Heales AACR 100% 100% 90% 90% 80% 80% 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% 0 6 12 18 24 30 36 42 48 0 6 12 18 24 30 36 42 48 CT based 59 35 13 7 6 3 2 1 1 CTbased 59 52 42 29 25 16 15 , 3 Palbociclib+ET 61 43 32 27 23 15 8 6 3 61 52 42 37 33 25 19 15 9 PFS months Overall Survival months Palbociclib + ET CT Palbeciclib + ET CT PFS events, N (%) 40 (65.6) 50 (84.7) os events, N (%) 25 (41.0) 24 (40.7) Median PFS months 18.7 7.8 Median OS months 46.1 36.8 HR 0.45 95% CI (0.29-0.70). p<0.001 (log-rank) Proportional hazard cannot be assumed GBG PADMA The presentation H the property of the Contact these at Tar X

Oncology Brothers @OncBrothers

PADMA Data

1.3K impressions · 12 likes · Dec 11, 2024

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[Slide 1] San Antonio Breast Cancer Symposium December 10-13. 2024 SAN ANTONIO BREAST CANCER SYMPOSIUM PADMA Study Design UT Health AACR - Patient Population N=150 Arm A Endocrine therapy (ET) + HR-positive/HER2-negative palbociclib Female or male Indication for mono-chemotherapy No prior treatment for 1:1 metastatic/relapsed disease R No asymptomatic bone-only, oligo- metastatic disease Chemotherapy (CT) of No uncontrolled/untreated CNS Arm B physician's choice + ET metastases maintenance therapy Live-expectancy >6 months Stratification: ET with palbociclib: Al or fulvestrant + GnRHa - Endocrine resistant vs endocrine sensitive ET maintenance tamoxifen, Al or fulvestrant I GnRHa - Symptomatic vs asymptomatic metastatic disease CT: paclitaxel, capecitabine, epirubicin, or vinorelbine GBG PADMA This presentation is the intellectual property of the author/presenter Contact them at publications@gbg de for permission to reprint and/or distribute.

M. Bolton @5_utr

PADMA Data

1.1K impressions · 7 likes · Nov 26, 2024

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[Slide 1] LB1-03: Primary results of the randomised Phase III trial comparing first-line ET plus palbociclib vs standard mono-chemotherapy in women with high risk HER2-/HR+ metastatic breast cancer and indication for chemotherapy - PADMA study Presenting Author(s) and Co-Author(s): Sibylle Loibl Abstract Number: SESS-3616 Background: Whether chemotherapy (CT) or an endocrine therapy (ET) in combination with a CDK4/6 inhibitor in HR+/HER2-metastatic breast cancer (mBC) is the preferred option is still a matter of debate. The PADMA (NCT03355157; GBG 93) prospective, randomized, open- label, multi-center, phase III trial is the first trial to compare a standard mono-CT followed by maintenance ET with a CDK4/6 inhibitor plus ET as first-line therapy in high -risk mBC patients (pts). Study Design: Pts previously untreated for HR+/HER2- mBC with an indication for chemotherapy were randomized to receive either palbociclib 125mg on days 1-21 q28 in combination with ET (palb/ET) or to mono-CT of physicians choice (PC) with or without following maintenance ET. Stratification factors included endocrine resistance and presence of disease symptoms as defined by the investigator. Treatment was administered until disease progression, unacceptable toxicity, withdrawal of consent, or modification to the initial treatment plan. The primary endpoint (EP) is time to treatment-failure (TTF) defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patients preference, or death. Secondary EPs included progression free survival (PFS), time to first subsequent treatment (TFST), time to first subsequent chemotherapy, time to second subsequent treatment regimen, overall survival (OS), safety, compliance, and well-being and health care utilization by daily monitoring content with quality of life, degree of bother by side-effects, number and duration of phone calls, site visits. Results: A total of 130 pts (66 palb/ET; 64 CT) were enrolled at 28 German sites between Apr 2018 and Dec 2023 of whom 120 started treatment and were included in this analysis. 12 (10%) of the pts were pre-/perimenopausal, 90 (75%) had metastases in two or more organ systems, 52 (43.3%) had symptomatic disease, 10 (8.3%) were endocrine resistant at enrolment. The median age was 62 (range 31-85) years. CT of PC was capecitabine 40 (69.0%), paclitaxel 17 (29.3%) and vinorelbine 1 (1.7%). Out of 58 pts receiving CT, 13 pts (22.4%) switched to maintenance ET. After a median follow-up of 36.8 (15.0-47.7) months (mo) 45 pts (73.8%) in the palb/ET arm and 55 (93.2%) in the CT arm experienced a TTF event. The median TTF was significantly longer with palb/ET 17.2 (7.2, 25.9) mo vs 6.1 (4.3, 8.8) mo with CT (HR 0.46 [80% CI 0.35-0.60], log-rank p=0.0002) meeting its primary EP. The leading cause of treatment failure was progression (52.5% with palb/ET VS 76.3% with CT). Median PFS was significantly longer with palb/ET 18.7 (10.6, 29.1) mo and 7.8 (6.0, 10.0) mo with CT (HR 0.45 [95% CI 0.29-0.70], log-rank p=0.0002). Median TFST was significantly longer with

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PADMA Top Tweets

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Sara Tolaney@stolaney1

PADMA study: ET + palbo vs chemo (cape/taxane/navelbine) in high risk HR+ MBC--> confirms ET+ cdk4/6i is 1L SOC n=150 42% w/liver mets 6% BRCAm TTF: 17.2 vs 6.1mo HR 0.46 PFS: 18.7 vs 7.8...

👁 11.9K ♡ 112 ↻ 40 Dec 11, 2024

Oncology Brothers@OncBrothers

#SABCS24 Part 2: Highlights w/ @jamecancerdoc ✅ #EUROPA ✅ #TAILORx ✅ #PADMA ✅ #EMBER3 Full 📢: ...

👁 5.4K ♡ 38 ↻ 9 Jan 16, 2025

Hope Rugo@hoperugo

Sibylle Loibl presents Padma. Palbo plus ET improved TTF and PFS with OS trend compared to chemo. Patients should not get chemo first except in extraordinary situations. @OncoAlert...

👁 4.1K ♡ 54 ↻ 26 Dec 11, 2024

Erika Hamilton, MD@ErikaHamilton9

#PADMA study presented by Dr. Loibl - looking at induction chemo followed by ET maint vs. upfront ET + CDk4/6 Another study- chemo inferior to ET + CDK4/6. 🆘 No need to do this...

👁 2.6K ♡ 33 ↻ 11 Dec 11, 2024

Elisa Agostinetto@ElisaAgostinett

At #SABCS24 LBA session - @LoiblSibylle on the PADMA trial comparing 1st line ET + Palbo vs Standard Mono-CT in High Risk HER2-/HR+ metastatic BC and indication for...

👁 2.4K ♡ 16 ↻ 5 Dec 11, 2024

Harold J. Burstein, MD, PhD, FASCO@DrHBurstein

Padma study shows that first line treatment of ER+ MBC is >> better than first line single agent chemo. ⁦@SABCSSanAntonio⁩ #sabcs24

👁 2.0K ♡ 31 ↻ 7 Dec 11, 2024

Dr Amol Akhade@SuyogCancer

PADMA trial . Results similar to right choice trial . Not many pts with viceral crisis though. @Larvol @5_utr @OncoAlert @SABCSSanAntonio...

👁 1.7K ♡ 20 ↻ 5 Dec 11, 2024

Oncology Brothers@OncBrothers

2. #PADMA: Ph III, HR+ metastatic breast cancer, chemo vs ET + Palbociclib. - #SABCS22 in #RightChoice study, we knew CDK4/6i upfront is better. -...

👁 1.3K ♡ 12 ↻ 2 Dec 11, 2024

M. Bolton@5_utr

PADMA: High risk HR+/Her2- metastatic breast cancer -> physicians choice chemo + endocrine vs endocrine + palbociclib mOS was “numerically prolonged” p=0.46 Much higher high grade heme...

👁 1.1K ♡ 7 ↻ 0 Nov 26, 2024

Gaia Griguolo@GaiaGriguolo

PADMA trial presented at #SABCS24 today Results supporting international guidelines advocating use of ET+CdK4/6i as standard first-line treatment for HR+mBC #bcsm...

👁 1.1K ♡ 15 ↻ 7 Dec 11, 2024

Trial Background

About the PADMA Trial

PADMA is a Phase IV, prospective, randomized, open-label, multicenter trial that is the first study to directly compare palbociclib (Ibrance) plus endocrine therapy against standard single-agent chemotherapy as first-line treatment for high-risk HR+/HER2- metastatic breast cancer. Conducted across 28 sites in Germany, the trial enrolled 130 patients with an indication for mono-chemotherapy. The results, presented at SABCS 2024, demonstrated that palbociclib plus endocrine therapy is significantly superior to chemotherapy, supporting existing international guidelines.

ClinicalTrials.gov

Regulatory Milestone

FDA Approval

FDA APPROVED Ibrance (palbociclib) — 1L HR+/HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy (accelerated approval Feb 2015; regular approval with expanded label Feb 2016). PADMA is a confirmatory trial supporting CDK4/6i + ET over chemotherapy.

Palbociclib (Ibrance) received initial accelerated FDA approval on February 3, 2015, in combination with letrozole for first-line HR+/HER2- metastatic breast cancer. Regular approval with expanded indication to any AI was granted February 19, 2016. In April 2019, approval was expanded to include men. PADMA is not a registrational trial but provides confirmatory real-world evidence supporting the guideline recommendation of ET + CDK4/6i over chemotherapy.

Source: FDA Press Release

Study Design

Trial Methodology & Results

Study Design

Phase IV, prospective, randomized 1:1, open-label, multicenter trial (NCT03355157; GBG 93). Patients were stratified by endocrine resistance vs. sensitivity and symptomatic vs. asymptomatic metastatic disease. Treatment continued until disease progression, unacceptable toxicity, withdrawal, or treatment plan change.

Population

Previously untreated female and male patients with high-risk HR+/HER2- metastatic breast cancer with a clinical indication for mono-chemotherapy. Required life expectancy greater than 6 months. Excluded asymptomatic bone-only disease, oligo-metastatic disease, and uncontrolled CNS metastases. Median age 62 years; approximately 42% had liver metastases and 32% were ET-resistant.

Interventions

Palbociclib 125 mg on days 1-21 of every 28-day cycle plus endocrine therapy (aromatase inhibitor or fulvestrant) versus mono-chemotherapy of physician's choice (capecitabine, paclitaxel, or vinorelbine) with or without subsequent maintenance ET.

Primary Endpoints

Primary endpoint: Time to treatment failure (TTF), defined as time from randomization to discontinuation due to disease progression, toxicity, patient preference, or death. Secondary endpoints: PFS, OS, time to first subsequent treatment, safety, tolerability, treatment compliance, patient-reported QoL, and DMTI.

Progression-Free Survival (PFS)

Palbociclib plus ET demonstrated a highly significant improvement in PFS versus chemotherapy. Median PFS was 18.7 months vs. 7.8 months (HR 0.45; 95% CI: 0.29-0.70; p<0.001). The primary endpoint TTF was also significantly improved: median TTF 17.2 months vs. 6.1 months (HR 0.46; 95% CI: 0.31-0.69; p<0.001). Disease progression was the leading cause of treatment failure: 52.5% in the palbociclib arm vs. 76.3% in the chemotherapy arm.

PFS HR 0.45 — 18.7 vs. 7.8 months

Source: FDA Ibrance Approval

Overall Survival (OS)

There was a numerical trend toward improved OS favoring palbociclib plus ET, though not statistically significant. Median OS was 46.1 months vs. 36.8 months in the chemotherapy arm (HR 0.81; 95% CI: 0.46-1.43; p=0.4630). Proportional hazards could not be assumed for the OS data.

Source: PADMA Trial - SABCS 2024

Safety & Tolerability

Hematologic toxicity was significantly higher in the palbociclib arm: any-grade hematologic TRAEs 96.8% vs. 58.6% (p<0.001), Grade 3-4 hematologic TRAEs 54.8% vs. 6.9%. Non-hematologic adverse events were comparable between groups (82.3% vs. 93.1%). Overall Grade 3-4 TRAEs were 59.7% vs. 27.6%. Only 3 patients discontinued palbociclib due to adverse events. One treatment-related death (septic shock) occurred in the palbociclib arm.

Higher hematologic toxicity but low AE-driven discontinuation

Source: Ibrance Prescribing Information

Clinical Implications

PADMA provides the first prospective, randomized evidence that CDK4/6 inhibitor-based endocrine therapy is superior to chemotherapy in high-risk HR+/HER2- mBC patients with an indication for chemotherapy. The results reinforce existing international guidelines recommending ET plus CDK4/6 inhibitors as standard first-line treatment. The patient-centric TTF endpoint captured broader clinical benefit including tolerability and treatment durability. While OS was numerically favored, longer follow-up is needed.

Frequently Asked Questions

PADMA FAQ

What is the PADMA trial?

PADMA (NCT03355157) is a randomized, open-label, multicenter Phase IV trial from the German Breast Group (GBG) comparing first-line palbociclib (Ibrance) plus endocrine therapy against chemotherapy in patients with HR-positive, HER2-negative metastatic breast cancer who had an indication for chemotherapy. It provides prospective, randomized head-to-head data for these two first-line strategies.

What did PADMA show?

Palbociclib plus endocrine therapy significantly improved median progression-free survival to 18.7 versus 7.8 months with chemotherapy (hazard ratio 0.45; 95% CI 0.29-0.70; p<0.001), with time to treatment failure of 17.2 versus 6.1 months. Overall survival showed a numerical trend favoring palbociclib plus endocrine therapy (46.1 versus 36.8 months) that was not statistically significant.

Is palbociclib (Ibrance) FDA approved?

Yes. Palbociclib (Ibrance, Pfizer) is FDA-approved in combination with endocrine therapy for HR-positive, HER2-negative advanced or metastatic breast cancer. PADMA itself is an investigator-initiated randomized comparison of palbociclib plus endocrine therapy versus chemotherapy and is not a separate FDA registration trial.

How did safety compare between palbociclib plus endocrine therapy and chemotherapy?

Hematologic toxicity was more common with palbociclib plus endocrine therapy (any-grade hematologic treatment-related adverse events 96.8% versus 58.6%; grade 3-4 54.8% versus 6.9%), while non-hematologic adverse events were comparable between the arms. The palbociclib hematologic events, chiefly neutropenia, are generally manageable with monitoring and dose adjustment.

Why is PADMA clinically important?

PADMA provides prospective, randomized evidence that CDK4/6 inhibitor-based endocrine therapy is superior in progression-free survival to chemotherapy as first-line treatment in high-risk HR-positive, HER2-negative metastatic breast cancer patients who otherwise had a chemotherapy indication, reinforcing guideline preference for endocrine therapy plus a CDK4/6 inhibitor.

Major Media & Publications

PADMA in the News

FDA

FDA Approves Palbociclib (Ibrance) for HR+/HER2- Metastatic Breast Cancer

FDAFeb 2015

Publication

PADMA Trial: First-Line Palbociclib + ET vs. Chemotherapy in High-Risk HR+/HER2- mBC

SABCS 2024Dec 2024

Media Coverage

PADMA Trial Shows CDK4/6i-Based Therapy Superior to Chemotherapy in High-Risk mBC

Oncology News CentralDec 2024

Press Release

Pfizer Receives Expanded FDA Approval for Ibrance in HR+/HER2- mBC

PfizerFeb 2016

Physician Opinions

Key KOL Sentiments - PADMA

Doctor	Sentiment	Comment
Hope Rugo @hoperugo	● POSITIVE	Sibylle Loibl presents Padma. Palbo plus ET improved TTF and PFS with OS trend compared to chemo. Patients should not get chemo first except in extraordinary situations. @OncoAlert #SABCS24 https://t.co/kwm70GQRxi
Erika Hamilton, MD @ErikaHamilton9	● POSITIVE	#PADMA study presented by Dr. Loibl - looking at induction chemo followed by ET maint vs. upfront ET + CDk4/6 Another study- chemo inferior to ET + CDK4/6. 🆘 No need to do this folks. Chemo 🚫doesn't help us here. #SABCS24 @SABCSSanAntonio https:/
Elisa Agostinetto @ElisaAgostinett	● POSITIVE	At #SABCS24 LBA session - @LoiblSibylle on the PADMA trial comparing 1st line ET + Palbo vs Standard Mono-CT in High Risk HER2-/HR+ metastatic BC and indication for CT ⬆️TTF and PFS w/palbo+ET Reassuring data supporting 1st line CDK4/6i+ET as SoC
Harold J. Burstein, MD, PhD, FASCO @DrHBurstein	● POSITIVE	Padma study shows that first line treatment of ER+ MBC is >> better than first line single agent chemo. ⁦@SABCSSanAntonio⁩ #sabcs24 https://t.co/OeGem0qJtn
Oncology Brothers @OncBrothers	● POSITIVE	2. #PADMA: Ph III, HR+ metastatic breast cancer, chemo vs ET + Palbociclib. - #SABCS22 in #RightChoice study, we knew CDK4/6i upfront is better. - Time to treatment failure and PFS better in PADMA. CDK4/6i remain 1L SoC for these pts 3/5 https://t
Gaia Griguolo @GaiaGriguolo	● POSITIVE	PADMA trial presented at #SABCS24 today Results supporting international guidelines advocating use of ET+CdK4/6i as standard first-line treatment for HR+mBC #bcsm @OncoAlert https://t.co/GfGcwTud8E
Moffitt Cancer Center @MoffittNews	● POSITIVE	Latest from #SABCS24: Sibylle Loibl, MD, presents results from the PADMA Phase III trial, showing that palbociclib + endocrine therapy significantly improves time to treatment failure and progression-free survival over chemotherapy in high-risk HER2-
Jos Sandoval @JLSandoval	● POSITIVE	PADMA study (ET+Palbo vs Chemo as 1L in MBC w/ indication for 1L chemo). Increased TTF & PFS w/ 1L ET+Palbo. Similar OS. Similar results to Right Choice w/ Ribo. Soon results from AMBER w/ Abema. Yet, evidence seems to support ET+CDK4/6i as 1L in
Sara Tolaney @stolaney1	● NEUTRAL	PADMA study: ET + palbo vs chemo (cape/taxane/navelbine) in high risk HR+ MBC--> confirms ET+ cdk4/6i is 1L SOC n=150 42% w/liver mets 6% BRCAm TTF: 17.2 vs 6.1mo HR 0.46 PFS: 18.7 vs 7.8 mo, HR 0.45 OS trend: 46.1 vs 36.8 mo #SABCS24 @OncoAler
Dr Amol Akhade @SuyogCancer	● NEUTRAL	PADMA trial . Results similar to right choice trial . Not many pts with viceral crisis though. @Larvol @5_utr @OncoAlert @SABCSSanAntonio #SABCS24 https://t.co/Q0xYG7OMIn
M. Bolton @5_utr	● NEUTRAL	PADMA: High risk HR+/Her2- metastatic breast cancer -> physicians choice chemo + endocrine vs endocrine + palbociclib mOS was “numerically prolonged” p=0.46 Much higher high grade heme toxicity 56.5% vs 10.3%, worse with palbociclib/endocrine
Armando Orlandi @ArmandOrlandi	● NEUTRAL	Cowabunga! Riding Breast Cancer's Biggest Data’s Wave 🏄🏻‍♂️🌊🤙🏻from #SABCS24 🎯 PADMA Phase III confirms what we already knew: CDK4/6i+ET is the way! Even in high-risk HR+/HER2- mBC with 'chemo indication' • TTF: 17.2 vs 6.1 mo • PFS: 18.7 vs 7.8 mo
German Breast Group @GBG_Forschung	● NEUTRAL	🌟 Highlights from #SABCS24: #PADMA Trial Results First prospective, randomized Phase IV trial comparing endocrine therapy (#ET) + CDK4/6 inhibitor with standard mono-#chemotherapy (± maintenance ET) as first-line #treatment for high-risk HR+/HER2- m
Paul Hughes PharmD, PA-C @paulhughes314	● NEUTRAL	@ErikaHamilton9 @SABCSSanAntonio When trial criteria specifies “indication for chemotherapy” does this mean patients are in visceral crisis? Trying to understand patient population and how this applies to US practice
Dr Michael Copeman @drmcopeman	● NEUTRAL	@ArmandOrlandi @OncoAlert @SABCSSanAntonio Outside clinical trials (with highly treatment-adherent patients, closely monitored), we need to find ways to improve compliance with CDK4/6 inhibitors plus endocrine therapies. Patients need interim goals

PADMA Trial

PADMA Key Takeaways

Top KOLs Discussing PADMA

PADMA Key Slides & Visuals

PADMA Top Tweets

About the PADMA Trial

FDA Approval

Trial Methodology & Results

Study Design

Population

Interventions

Primary Endpoints

Progression-Free Survival (PFS)

Overall Survival (OS)

Safety & Tolerability

Clinical Implications

PADMA FAQ

What is the PADMA trial?

What did PADMA show?

Is palbociclib (Ibrance) FDA approved?

How did safety compare between palbociclib plus endocrine therapy and chemotherapy?

Why is PADMA clinically important?

PADMA in the News

Key KOL Sentiments - PADMA

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