- Email: [email protected]
Comparative effectiveness of palbociclib plus letrozole vs letrozole for metastatic breast cancer in US real-world clinical practices
abstracts
Annals of Oncology
Table: 327P Real-world progression-free survival (rwPFS) by subgroups Median rwPFS (months)
95%CI
878
21.9
20.1 – 28.2
407 294 177
21.8 21.4 28.6
18.8—26.4 16.1—29.9 20.1—NE
587 62 18 28 183
22.6 NE 13.8 NE 19.9
20.3—28.6 11.3—NE 7.8—NE 5.9—NE 16.1—NE
67 811
19.5 22.4
14.3—25.9 20.2—28.7
311 119 359 89
21.9 21.0 22.2 26.5
17.6—33.1 13.1—28.6 19.5—32.7 15.5—NE
322 225 623 255 446 432
22.4 21.0 17.3 NE 14.8 33.1
18.9—NE 16.5—28.3 14.6—20.2 NE 12.7—18.3 28.3—NE
Lilly. M. De Laurentiis: Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Celgene; Honoraria (institution), Advisory / Consultancy: AstraZeneca. C. Zamagni: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Morphotek; Research grant / Funding (institution): Roche/ Genentech. M. Agterof: Advisory / Consultancy: Roche. M. Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy: Puma; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Roche-Genentech; Advisory / Consultancy: Taiho Oncology. All other authors have declared no conflicts of interest.
329P
Comparative effectiveness of palbociclib plus letrozole vs letrozole for metastatic breast cancer in US real-world clinical practices
R.M. Layman1, X. Liu2, J. Mardekian3, L. McRoy4 1 Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2US Medical Affairs, Pfizer Inc, Peapack, NJ, USA, 3Statistics, Pfizer Inc, New York, NY, USA, 4Global Medical Affairs, Pfizer Inc, New York, NY, USA Inc.
328P
Ribociclib (RIB) plus letrozole (LET) in male patients (pts) with hormone receptor-positive (HR1), human epidermal growth factor receptor-2– negative (HER2–) advanced breast cancer (ABC) from the CompLEEment-1 trial
M. Campone1, M. De Laurentiis2, C. Zamagni3, I. Kudryavcev4, M. Agterof5, U. BrownGlaberman6, M. Palacova7, S. Chatterjee8, L. Menon-Singh9, J. Wu10, K. Zhou11, M. Martin12 1 Medical Oncology, Institute of Cancer Research in Western France (ICO), Nantes, France, 2Surgical Oncology, IRCCS Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy, 3Medical Oncology, The Bologna University Hospital Authority St. OrsolaMalpighi Polyclinic, Bologna, Italy, 4Medical Oncology, Kaluga Regional Clinical Oncology Center, Kaluga, Russian Federation, 5Lokatie Utrecht Leidsche Rijn, St. Antonius Hospital, Utrecht/Nieuwegein, Netherlands, 6Division of Haematology/ Oncology, University of New Mexico Cancer Center, New Mexico, NM, USA, 7Medicine, Masaryk Memorial Cancer Institute, Brno, Czech Republic, 8Medical Oncology, Tata Medical Centre, Kolkata, India, 9Global Medical Affairs, Novartis, East Hanover, NJ, USA, 10 Oncology Medical Affairs, Novartis, East Hanover, NJ, USA, 11Med, Novartis, East Hanover, NJ, USA, 12Medical Oncology, Hospital General Universitario Gregorio Mara~ non, Madrid, Spain Background: There is an unmet need to assess efficacy and safety of therapies for ABC in men. The cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor RIB has been approved for use in combination with LET for the treatment of HRþ, HER2– ABC in
Volume 30 | Supplement 5 | October 2019
Background: Palbociclib, the first clinically available oral CDK4/6 inhibitor, in combination with endocrine therapy has become standard of care for HRþ/HER2- advanced/ metastatic breast cancer (MBC). No real-world studies have examined relative effectiveness of palbociclib plus endocrine therapy compared with endocrine therapy alone. This study compared real-world progression free survival (rwPFS) of palbociclib plus letrozole (PBþLE) vs letrozole alone (LE) for MBC in US routine clinical practices. Methods: We conducted a retrospective analysis of MBC patients from the Flatiron Health longitudinal database, which contains electronic health records from 275 cancer clinics representing more than 2 million actively treated cancer patients in the US. Between February 2015 and August 2018, 1416 HRþ/HER2– MBC women started PBþLE (n ¼ 798) or LE (n ¼ 618) as first-line therapy. Patients were evaluated from start of PBþLE or LE to November 2018, death, or last visit, whichever came first. rwPFS was defined as months from start of PBþLE or LE to death or disease progression based on clinical assessment or evidence by radiographic scan/tissue biopsy. 1:1 propensity score (PS) matching was used to balance patient characteristics. Results: Of 1416 eligible patients, 906 were 1:1 PS matched (453 for each cohort). Median follow-up was 16.8 months, median age was 68.0 years, 70% were white, and 49.7% had visceral disease. Median rwPFS was 24.5 months (95%CI ¼ 20.7 – 32.7) in PBþLE cohort and 17.1 months (95%CI¼13.7—19.8) in LE cohort (HR ¼ 0.68, 95%CI¼0.56—0.84, p ¼.0003). Table presents key patient characteristics and landmark rwPFS rates. Conclusions: The first comparative analysis of a CDK4/6 inhibitor in combination with endocrine therapy compared to endocrine therapy alone provides real-world evidence confirming the findings of PFS benefit demonstrated in clinical trial data for palbociclib in diverse clinical practices.
doi:10.1093/annonc/mdz242 | v115
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.024/5577001 by guest on 24 October 2019
All patients Age, year 18-64 65-74 75 Ethnicity White Black Asian Hispanic Other/unknown Menopausal status Premenopausal (Age50) Postmenopausal (Age>50) Disease stage at initial diagnosis 1 or 2 3 4 (De novo) Unknown ECOG Score 0 1þ No bone-only disease Bone-only disease Visceral disease Nonvisceral disease No# of metastic sites
N
men and postmenopausal women with no prior therapy for advanced disease. Here we present a subgroup analysis of male pts in CompLEEment-1, an open-label, phase 3b trial evaluating RIB þ LET as first-line therapy in a pt population with broad inclusion/ exclusion criteria to reflect real-world practice. Methods: Pts with HRþ, HER2– ABC and no prior hormonal therapy for ABC received RIB (600 mg daily [QD], 3 weeks on/1 week off) þ LET (2.5 mg QD, continuous), and concomitant goserelin or leuprolide. Safety and tolerability (primary outcome), overall response rate (ORR), and clinical benefit rate (CBR) were analyzed for male pts in a subgroup analysis. Results: There were 39 men in the study. The median follow-up was 10.35 months, and the median duration of exposure to RIB was 8.0 months. Any-grade adverse events (AEs) were reported in 38 pts; 36 AEs were treatment-related. Serious AEs (SAEs) were reported in 4 pts; 1 SAE was related to treatment. No fatal treatment-related SAEs were reported. Most common any-grade AEs ( 20%) were neutropenia (n ¼ 14), hot flush (n ¼ 12), diarrhea (n ¼ 10), and fatigue (n ¼ 8). There were 31 pts with at least 1 dose adjustment of RIB; 5 reductions and 27 interruptions were due to AEs. Fourteen pts permanently discontinued treatment: 7 due to progressive disease and 4 due to AEs. ORR in pts with measurable disease was 34.4% (95% confidence interval [CI], 18.653.2%), and CBR was 68.8% (95% CI, 50.0-83.9%). Median TTP was not reached. Conclusions: This subgroup analysis from CompLEEment-1 supports the safety and efficacy of RIB þ LET in men with HRþ, HER2– ABC, and adds to the clinical understanding of CDK4/6 inhibitors in men with HRþ, HER2– ABC. Clinical trial identification: NCT02941926. Editorial acknowledgement: Medical editorial assistance was provided by Rob Camp, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study: Novartis. Funding: Novartis Pharmaceuticals. Disclosure: M. Campone: Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy:
abstracts
Annals of Oncology
Table: 329P Patient characteristics and real-world progressionfree survival (rwPFS) Variable
LE alone (N ¼ 453)
68.0 69.8 2.0 26.9 49.7 24.5 (20.7—32.7) 82.8 72.1 60.1 50.2 16.8(8.1—27.1)
68.0 70.6 2.0 32.2 49.7 17.1 (13.7—19.8) 74.5 58.9 48.4 39.1 16.8(6.9—26.9)
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.024/5577001 by guest on 24 October 2019
Median age (years) White (%) Median number of metastatic sites (n) Bone only disease (%) Visceral disease (%) Median rwPFS, months (95%CI) rwPFS rate at 6 months (%) rwPFS rate at 12 months (%) rwPFS rate at 18 months (%) rwPFS rate at 24 months (%) Median follow-up, months (IQR)
PBþLE (N ¼ 453)
PBþLE ¼ Palbociclib plus letrozole; LE ¼ Letrozole alone; IQR ¼ Interquartile Range
Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: R.M. Layman: Research grant / Funding (institution): Pfizer Inc. X. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. J. Mardekian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. L. McRoy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc.
v116 | Breast Cancer, Metastatic
Volume 30 | Supplement 5 | October 2019
Annals of Oncology
Table: 327P Real-world progression-free survival (rwPFS) by subgroups Median rwPFS (months)
95%CI
878
21.9
20.1 – 28.2
407 294 177
21.8 21.4 28.6
18.8—26.4 16.1—29.9 20.1—NE
587 62 18 28 183
22.6 NE 13.8 NE 19.9
20.3—28.6 11.3—NE 7.8—NE 5.9—NE 16.1—NE
67 811
19.5 22.4
14.3—25.9 20.2—28.7
311 119 359 89
21.9 21.0 22.2 26.5
17.6—33.1 13.1—28.6 19.5—32.7 15.5—NE
322 225 623 255 446 432
22.4 21.0 17.3 NE 14.8 33.1
18.9—NE 16.5—28.3 14.6—20.2 NE 12.7—18.3 28.3—NE
Lilly. M. De Laurentiis: Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Celgene; Honoraria (institution), Advisory / Consultancy: AstraZeneca. C. Zamagni: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Morphotek; Research grant / Funding (institution): Roche/ Genentech. M. Agterof: Advisory / Consultancy: Roche. M. Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy: Puma; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Roche-Genentech; Advisory / Consultancy: Taiho Oncology. All other authors have declared no conflicts of interest.
329P
Comparative effectiveness of palbociclib plus letrozole vs letrozole for metastatic breast cancer in US real-world clinical practices
R.M. Layman1, X. Liu2, J. Mardekian3, L. McRoy4 1 Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2US Medical Affairs, Pfizer Inc, Peapack, NJ, USA, 3Statistics, Pfizer Inc, New York, NY, USA, 4Global Medical Affairs, Pfizer Inc, New York, NY, USA Inc.
328P
Ribociclib (RIB) plus letrozole (LET) in male patients (pts) with hormone receptor-positive (HR1), human epidermal growth factor receptor-2– negative (HER2–) advanced breast cancer (ABC) from the CompLEEment-1 trial
M. Campone1, M. De Laurentiis2, C. Zamagni3, I. Kudryavcev4, M. Agterof5, U. BrownGlaberman6, M. Palacova7, S. Chatterjee8, L. Menon-Singh9, J. Wu10, K. Zhou11, M. Martin12 1 Medical Oncology, Institute of Cancer Research in Western France (ICO), Nantes, France, 2Surgical Oncology, IRCCS Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy, 3Medical Oncology, The Bologna University Hospital Authority St. OrsolaMalpighi Polyclinic, Bologna, Italy, 4Medical Oncology, Kaluga Regional Clinical Oncology Center, Kaluga, Russian Federation, 5Lokatie Utrecht Leidsche Rijn, St. Antonius Hospital, Utrecht/Nieuwegein, Netherlands, 6Division of Haematology/ Oncology, University of New Mexico Cancer Center, New Mexico, NM, USA, 7Medicine, Masaryk Memorial Cancer Institute, Brno, Czech Republic, 8Medical Oncology, Tata Medical Centre, Kolkata, India, 9Global Medical Affairs, Novartis, East Hanover, NJ, USA, 10 Oncology Medical Affairs, Novartis, East Hanover, NJ, USA, 11Med, Novartis, East Hanover, NJ, USA, 12Medical Oncology, Hospital General Universitario Gregorio Mara~ non, Madrid, Spain Background: There is an unmet need to assess efficacy and safety of therapies for ABC in men. The cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor RIB has been approved for use in combination with LET for the treatment of HRþ, HER2– ABC in
Volume 30 | Supplement 5 | October 2019
Background: Palbociclib, the first clinically available oral CDK4/6 inhibitor, in combination with endocrine therapy has become standard of care for HRþ/HER2- advanced/ metastatic breast cancer (MBC). No real-world studies have examined relative effectiveness of palbociclib plus endocrine therapy compared with endocrine therapy alone. This study compared real-world progression free survival (rwPFS) of palbociclib plus letrozole (PBþLE) vs letrozole alone (LE) for MBC in US routine clinical practices. Methods: We conducted a retrospective analysis of MBC patients from the Flatiron Health longitudinal database, which contains electronic health records from 275 cancer clinics representing more than 2 million actively treated cancer patients in the US. Between February 2015 and August 2018, 1416 HRþ/HER2– MBC women started PBþLE (n ¼ 798) or LE (n ¼ 618) as first-line therapy. Patients were evaluated from start of PBþLE or LE to November 2018, death, or last visit, whichever came first. rwPFS was defined as months from start of PBþLE or LE to death or disease progression based on clinical assessment or evidence by radiographic scan/tissue biopsy. 1:1 propensity score (PS) matching was used to balance patient characteristics. Results: Of 1416 eligible patients, 906 were 1:1 PS matched (453 for each cohort). Median follow-up was 16.8 months, median age was 68.0 years, 70% were white, and 49.7% had visceral disease. Median rwPFS was 24.5 months (95%CI ¼ 20.7 – 32.7) in PBþLE cohort and 17.1 months (95%CI¼13.7—19.8) in LE cohort (HR ¼ 0.68, 95%CI¼0.56—0.84, p ¼.0003). Table presents key patient characteristics and landmark rwPFS rates. Conclusions: The first comparative analysis of a CDK4/6 inhibitor in combination with endocrine therapy compared to endocrine therapy alone provides real-world evidence confirming the findings of PFS benefit demonstrated in clinical trial data for palbociclib in diverse clinical practices.
doi:10.1093/annonc/mdz242 | v115
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.024/5577001 by guest on 24 October 2019
All patients Age, year 18-64 65-74 75 Ethnicity White Black Asian Hispanic Other/unknown Menopausal status Premenopausal (Age50) Postmenopausal (Age>50) Disease stage at initial diagnosis 1 or 2 3 4 (De novo) Unknown ECOG Score 0 1þ No bone-only disease Bone-only disease Visceral disease Nonvisceral disease No# of metastic sites
N
men and postmenopausal women with no prior therapy for advanced disease. Here we present a subgroup analysis of male pts in CompLEEment-1, an open-label, phase 3b trial evaluating RIB þ LET as first-line therapy in a pt population with broad inclusion/ exclusion criteria to reflect real-world practice. Methods: Pts with HRþ, HER2– ABC and no prior hormonal therapy for ABC received RIB (600 mg daily [QD], 3 weeks on/1 week off) þ LET (2.5 mg QD, continuous), and concomitant goserelin or leuprolide. Safety and tolerability (primary outcome), overall response rate (ORR), and clinical benefit rate (CBR) were analyzed for male pts in a subgroup analysis. Results: There were 39 men in the study. The median follow-up was 10.35 months, and the median duration of exposure to RIB was 8.0 months. Any-grade adverse events (AEs) were reported in 38 pts; 36 AEs were treatment-related. Serious AEs (SAEs) were reported in 4 pts; 1 SAE was related to treatment. No fatal treatment-related SAEs were reported. Most common any-grade AEs ( 20%) were neutropenia (n ¼ 14), hot flush (n ¼ 12), diarrhea (n ¼ 10), and fatigue (n ¼ 8). There were 31 pts with at least 1 dose adjustment of RIB; 5 reductions and 27 interruptions were due to AEs. Fourteen pts permanently discontinued treatment: 7 due to progressive disease and 4 due to AEs. ORR in pts with measurable disease was 34.4% (95% confidence interval [CI], 18.653.2%), and CBR was 68.8% (95% CI, 50.0-83.9%). Median TTP was not reached. Conclusions: This subgroup analysis from CompLEEment-1 supports the safety and efficacy of RIB þ LET in men with HRþ, HER2– ABC, and adds to the clinical understanding of CDK4/6 inhibitors in men with HRþ, HER2– ABC. Clinical trial identification: NCT02941926. Editorial acknowledgement: Medical editorial assistance was provided by Rob Camp, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study: Novartis. Funding: Novartis Pharmaceuticals. Disclosure: M. Campone: Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy:
abstracts
Annals of Oncology
Table: 329P Patient characteristics and real-world progressionfree survival (rwPFS) Variable
LE alone (N ¼ 453)
68.0 69.8 2.0 26.9 49.7 24.5 (20.7—32.7) 82.8 72.1 60.1 50.2 16.8(8.1—27.1)
68.0 70.6 2.0 32.2 49.7 17.1 (13.7—19.8) 74.5 58.9 48.4 39.1 16.8(6.9—26.9)
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.024/5577001 by guest on 24 October 2019
Median age (years) White (%) Median number of metastatic sites (n) Bone only disease (%) Visceral disease (%) Median rwPFS, months (95%CI) rwPFS rate at 6 months (%) rwPFS rate at 12 months (%) rwPFS rate at 18 months (%) rwPFS rate at 24 months (%) Median follow-up, months (IQR)
PBþLE (N ¼ 453)
PBþLE ¼ Palbociclib plus letrozole; LE ¼ Letrozole alone; IQR ¼ Interquartile Range
Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: R.M. Layman: Research grant / Funding (institution): Pfizer Inc. X. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. J. Mardekian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. L. McRoy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc.
v116 | Breast Cancer, Metastatic
Volume 30 | Supplement 5 | October 2019