80O: Patient (pt) preference and satisfaction with the subcutaneous - - PowerPoint PPT Presentation

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80O: Patient (pt) preference and satisfaction with the subcutaneous fixed-dose combination

• f pertuzumab (P) and trastuzumab (H) in pts

with HER2-positive early breast cancer (HER2+ eBC): Interim analysis of the open-label, randomised cross-over PHranceSCa study

Joyce O'Shaughnessy,1 Susana Sousa,2 Josefina Cruz,3 Lesley Fallowfield,4 Päivi Auvinen,5 Catarina Pulido,6 Ana Cvetanovic,7 Sharon Wilks,8 Leonor Ribeiro,9 Mauricio Burotto,10 Dirk Klingbiel,11 Dimitri Messeri,11 Ari Alexandrou,12 Peter Trask,13 Judy Fredriksson,11 Ljiljana Stamatovic14

1Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA

; 2Department of Medical Oncology, Portuguese Oncology Institute of Porto, Porto, Portugal; 3Hospital Universitario de Canarias, La Laguna, S/C Tenerife, Spain;

4Brighton & Sussex Medical School, Falmer, UK; 5Cancer Center, Kuopio University Hospital, Kuopio, Finland; 6Centro de Oncologia, Hospital Da Luz Lisboa, Lisbon, Portugal; 7Medical Faculty Nis and Clinical Centre Nis, Nis, Serbia; 8Texas Oncology San A

ntonio, San A ntonio, TX, USA ; 9Centro Hospitalar Universitário Lisboa Norte/Hospital Santa Maria (CHULN/HSM), Lisbon, Portugal; 10Bradford Hill Clinical Research Center, Santiago, Chile; 11F. Hoffmann-La Roche Ltd, Basel, Switzerland; 12Roche Products Limited, Welwyn Garden City, UK; 13Genentech, Inc., South San Francisco, CA , USA ;

14Clinic for Medical Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia

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Access slides at: https://bit.ly/2Vqn13i JO’S reports consultancy/advisory roles for AbbVie, Agendia, Amgen, AstraZeneca, BMS, Celgene, Eisai, Genentech, Inc., Immunomedics, Ipsen, Lilly, Merck, Novartis, Odonate, Pfizer, Puma, Prime Oncology, F. Hoffmann-La Roche Ltd, Seattle Genetics and Daiichi Sankyo. SS reports funding for travelling, congresses, lectures and advisory boards from F. Hoffmann-La Roche Ltd, Novartis, Pfizer, Tesaro, AstraZeneca, MSD, Pierre Fabre and Eisai. JC reports speaker honoraria from GSK, AstraZeneca,

• F. Hoffmann-La Roche Ltd, Novartis, Pharmamar, Eisai, Lilly, Celgene, Astellas, Amgen and Pfizer, and consultant/advisory roles for

GSK, AstraZeneca, F. Hoffmann-La Roche Ltd, Novartis, Pharmamar, Eisai, Lilly, Celgene, Astellas, Amgen and Pfizer. LF reports honoraria from Pfizer, AstraZeneca, BMS, Lilly, Novartis, Genomic Health and Nanostring. CP reports public speaking for AstraZeneca, Grunenthal and Novartis, and writing engagements from AstraZeneca. SW reports payment for an advisory board from Seattle Genetics. LR reports payments for speaking and advisory boards from Roche Pharmaceuticals, Merck Serono, MSD, BMS, AstraZeneca and Pfizer, and for personal medical education and participation in congresses from BMS, Roche Pharmaceuticals, Merck Serono, Pfizer, Amgen and Pierre Fabre. MB reports payments for advisory boards, speaking at industry symposiums and consulting roles from F. Hoffmann-La Roche Ltd, MSD, BMS, AstraZeneca and Novartis. DK is an employee of, and owns stocks in,

• F. Hoffmann-La Roche Ltd. DM is an employee of F. Hoffmann-La Roche Ltd. AA is an employee of Roche Products Limited. PT is

an employee of, and owns stocks in, Genentech, Inc. JF is an employee of F. Hoffmann-La Roche Ltd. All authors have received support for third-party writing assistance for this presentation, furnished by Daniel Clyde, PhD, of Health Interactions, from

• F. Hoffmann-La Roche Ltd.

Funding for this study was provided by F. Hoffmann-La Roche Ltd.

Disclosures

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

Administration is less invasive and more rapid vs separate P + H IV infusions1–3

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PH FDC SC can potentially reduce patients’ time in the clinic and free up resources at the practice

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PROs are increasingly important for decision-making; PHranceSCa provides insights into patients’ perspectives on PH FDC SC and provides supportive information to the pivotal FeDeriCa PK study1

PH FDC SC combines P + H in one ready-to-use, fixed-dose combination vial for SC injection

P IV and H IV can be given in any order. The PH FDC SC maintenance dose observation period assumes that the loading dose injection is well tolerated; patients can be observed for longer at the discretion of the investigator, per local requirements. Administration/observation times vary according to local labels. * P IV loading dose if needed: 840 mg; maintenance: 420 mg. H IV loading dose if needed: 8 mg/kg; maintenance: 6 mg/kg. PH FDC SC loading dose if needed: P 1200 mg/H 600 mg in 15 mL; maintenance: P 600 mg/H 600 mg in 10 mL. 1. Tan A, et al. SABCS 2019 (Abstract PD4-07); 2. Herceptin SmPC 2019; 3. PERJETA SmPC 2019. H, trastuzumab; IV, intravenous; P, pertuzumab; PH FDC SC, pertuzumab–trastuzumab fixed-dose combination for subcutaneous use; PK, pharmacokinetic; PROs, patient-reported outcomes.

5 90 8 150 180 420 15 30 40 80 120 160 200 240 280 320 360 400 440 480 520 560 600 PH FDC SC P + H IV PH FDC SC P + H IV Time (minutes) Loading doses (max)* Maintenance doses (max)* P + H IV infusion PH FDC SC administration Observation time

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PHranceSCa is an open-label, randomised cross-over study evaluating patient preference for PH FDC SC vs PH IV (NCT03674112)

All patients were female; median age was 49 years. Adjuvant hormone therapy and radiotherapy for breast cancer were permitted. * P IV loading dose if needed: 840 mg; maintenance: 420 mg q3w. H IV loading dose if needed: 8 mg/kg; maintenance: 6 mg/kg IV q3w.

† PH FDC SC loading dose if needed: P 1200 mg/H 600 mg in 15 mL; maintenance: P 600 mg/H 600 mg in 10 mL q3w.

Loading doses were only required for patients who had ≥6 weeks since their last neoadjuvant dose of P + H IV at study entry, or had ≥6 weeks since their last study treatment during the study. Maintenance doseswere used for subsequent administrations or dose delays <6 weeks. eBC, early breast cancer; chemo, chemotherapy; H, trastuzumab; HCP, healthcare professional; HR, hormone receptor; HRQoL, health-related quality of life; IV, intravenous; NACT, neoadjuvant chemotherapy; P, pertuzumab; pCR, pathological complete response; PH FDC SC, pertuzumab–trastuzumab fixed-dose combination for subcutaneous use; PPQ, Patient Preference Questionnaire; q3w, every 3 weeks; SC, subcutaneous; TASQ, Therapy Administration Satisfaction Questionnaire.

HER2-positive eBC; completed neoadjuvant P + H + chemo + surgery Target N = 140

R 1:1

Primary objective: Patient preference for PH FDC SC Key secondary objectives: Patient satisfaction; patients’ choice of formulation for the continuation period; HRQoL, HCP perception on time/resource, safety and tolerability (including safety of switching from SC to IV formulations and vice-versa), efficacy Stratification factors:

• NACT regimen
• pCR vs non-pCR
• HR status

P + H lV* x 3 cycles PH FDC SC† x 3 cycles

F O L L O W

• U

P D1C3 TASQ D1C6 PPQ, TASQ

P + H lV* x 3 cycles PH FDC SC† x 3 cycles

Cross-over period Continuation period

Patient selected PH FDC SC or P + H IV for a total of 18 cycles

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At IA, >80% of patients preferred PH FDC SC regardless of sequencing

PPQ Q1: “All things considered, which method of administration did you prefer?”

Clinical cut-off: 19 August, 2019. 95% CI for PH FDC SC preference: 60.7–93.5; 63.9–95.5; 69.1–91.6, respectively.

• 1. Pivot X, et al. Ann Oncol 2014; 25:1979–1987.

* 118 patients randomised; 51 completed the cross-over period and had made their treatment continuation choice. CI, confidence interval; H, trastuzumab; IA, Interim analysis; IV, intravenous; P, pertuzumab; PH FDC SC, pertuzumab–trastuzumab fixed-dose combination for subcutaneous use; PPQ, Patient Preference Questionnaire; Q, question; SC, subcutaneous.

81 84 82 19 16 18 10 20 30 40 50 60 70 80 90 100 P + H IV→ PH FDC SC (n = 26) PH FDC SC→ P + H IV (n = 25) All patients (n = 51)* Patients (%) Preferred SC Preferred IV

• PPQ completion rate: 100%
• Main reasons for SC preference:
• “Less time in clinic

(38/86 responses; 44%)”

• “More comfortable

during administration (22/86 responses; 26%)”

• Results consistent with PrefHer1
• PPQ findings consistent with

treatment continuation choice: 84% PH FDC vs 16% P + H IV

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TASQ responses supportive of primary endpoint: 90% of patients were “very satisfied” or “satisfied” with PH FDC SC vs 67% with P + H IV at IA

H, trastuzumab; IA, interim analysis; IV, intravenous; P, pertuzumab; PH FDC SC, pertuzumab–trastuzumab fixed-dose combination for subcutaneous use; Q, question; SC, subcutaneous; TASQ, Therapy Administration Satisfaction Questionnaire.

50 76 63 31 24 27 15 8 4 2 10 20 30 40 50 60 70 80 90 100 P + H IV→ PH FDC SC (n = 26) PH FDC SC→ P + H IV (n = 25) All patients (n = 51) Patients (%)

TASQ-SC

35 16 25 42 40 41 23 40 31 4 2 10 20 30 40 50 60 70 80 90 100 P + H IV→ PH FDC SC (n = 26) PH FDC SC→ P + H IV (n = 25) All patients (n = 51) Patients (%)

TASQ-IV

Very satisfied Satisfied Neither satisfied nor dissatisfied Dissatisfied Very dissatisfied

TASQ Q1: “How satisfied or dissatisfied were you with the SC injection/IV infusion?”

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Safety: Profile of PH FDC SC consistent with previous studies with P + H IV; no new safety signals identified when switching formulations at IA

* Including the continuation period, 81/116 patients (70%) experienced AEs; 16 (14%) had diarrhoea, which was mainly low-grade.

• 1. Pivot X, et al. Ann Oncol 2014; 25:1979–1987.

AE, adverse event; H, trastuzumab; IA, interim analysis; IV, intravenous; P, pertuzumab; PH FDC SC, pertuzumab–trastuzumab fixed-dose combination for subcutaneous use; SC, subcutaneous.

Patients with ≥1 of the following, n (%) P + H IV→ PH FDC SC PH FDC SC→ P + H IV All patients (n = 116) P + H IV Cycles 1–3 (n = 56) PH FDC SC Cycles 4–6 (n = 33) PH FDC SC Cycles 1–3 (n = 60) P + H IV Cycles 4–6 (n = 32) AE 35 (63) 22 (67) 35 (58) 14 (44) 80 (69)* Most common AEs (in >5% of patients) Local injection site reaction Radiation skin injury Diarrhoea Hot flush 11 (20) 9 (16) 3 (5) 6 (18) 2 (6) 5 (15) 2 (6) 15 (25) 6 (10) 4 (7) 2 (3) 5 (16) 21 (18) 24 (21) 15 (13)* 7 (6) Systemic infusion reaction Systemic injection reaction 3 (5) 1 (3) 1 (2) 3 (3) 2 (2)

• AE rates before and after switching were similar (P + H IV→PH FDC SC: 63%→67%; PH FDC SC→P + H IV: 58%→44%), consistent with PrefHer1
• No fatal AEs, no AEs leading to study discontinuation in either arm
• Only five grade ≥3 AEs (P + H IV: Ejection fraction decrease, lymphopenia; PH FDC SC: Ejection fraction decrease, diarrhoea, device-related infection)
• Only one serious AE (grade 1 pyrexia during P + H IV administration in the cross-over period)
• Only one cardiac event (grade 1 arrythmia during PH FDC SC administration in the cross-over period)
• Two patients experienced administration-related reactions related to hypersensitivity, both during PH FDC SC administration in the cross-over period and grade 1/2

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 Eighty-two percent of patients preferred PH FDC SC over P + H IV  Main reasons for PH FDC SC preference consistent with PrefHer1  “Less time in clinic”  “More comfortable during administration”  TASQ results supported patient preference  More patients were “very satisfied” or “satisfied” with PH FDC SC administration vs P + H IV  Most patients (84%) chose PH FDC SC to complete their treatment  PH FDC SC was generally well tolerated  Safety profile consistent with P + H IV1,2  No new safety signals seen, including when switching formulations  Primary analysis expected Quarter 4 2020

PHranceSCa IA summary

1.

• 1. Pivot X, et al. Ann Oncol 2014; 25:1979–1987; 2. Ismael G, et al. Lancet Oncol 2012; 13:869–878.

H, trastuzumab; IV, intravenous; IA, interim analysis; P, pertuzumab; PH FDC SC, pertuzumab–trastuzumab fixed-dose combination for subcutaneous use;

2.

TASQ, Therapy Administration Satisfaction Questionnaire.

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We would like to thank all the patients who participated in the trial, and their families, the investigators, clinicians and research staff at the 32 centres in 12 countries

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Support for third-party writing assistance for this presentation, furnished by Daniel Clyde, PhD,

• f Health Interactions, was provided by F. Hoffmann-La Roche Ltd

Thank you!