Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer

Abstract

Background: We assessed health-related quality of life (symptoms of therapy/patient functioning/global health status), in APHINITY (pertuzumab/placebo, trastuzumab, and chemotherapy as adjuvant HER2-positive early breast cancer therapy).

Methods: Patients received 1 year/18 cycles of pertuzumab/placebo with trastuzumab and chemotherapy and completed EORTC QLQ-C30 and BR23 questionnaires until 36 months post-randomisation/disease recurrence. Changes ≥10 points from baseline were considered clinically meaningful.

Results: 87-97% of patients completed questionnaires. In the pertuzumab versus placebo arms, mean decrease in physical function scores (baseline → end of taxane) was -10.7 (95% CI -11.4, -10.0) versus -10.6 (-11.4, -9.9), mean decrease in global health status was -11.2 (-12.2, -10.2) versus -10.2 (-11.1, -9.2), and mean increase in diarrhoea scores (baseline → end of taxane) was +22.3 (21.0, 23.6) versus +9.2 (8.2, 10.2). Diarrhoea scores remained elevated versus baseline in the pertuzumab arm throughout HER2-targeted treatment (week 25: +13.2; end of treatment: +12.2). Role functioning was maintained in both arms.

Conclusions: Improved invasive disease-free survival achieved by adding pertuzumab to trastuzumab and chemotherapy did not adversely affect the ability to conduct activities of daily living versus trastuzumab and chemotherapy alone. Patient-reported diarrhoea worsened during taxane therapy in both arms, persisting during HER2-targeted treatment in the pertuzumab arm. CLINICALTRIALS.GOV: NCT01358877.

Conflict of interest statement

All authors received support for third-party writing assistance for this manuscript, provided by F. Hoffmann-La Roche Ltd. J.Bi. reports consulting/advisory roles for AbbVie, Genomic Health, Libbs, Lilly, Pfizer, F. Hoffmann-La Roche Ltd, and travel/accommodations/expenses from AstraZeneca and F. Hoffmann-La Roche Ltd. E.C. is an employee of Roche Products Limited and is named on issued patent ‘Uses for and article of manufacture including HER2 dimerisation inhibitor pertuzumab, 13/649591’. C.B. is a freelance pharmaceutical physician/medical advisor with Barton Oncology Ltd and has undertaken paid consultancy work with Roche Products Limited and many other companies and organisations, including (in the last ~5 years) Apeiron Biologics AG, Cancer Research UK Centre for Drug Development, Cancer Targeting Systems Inc, CellCentric Ltd, Certara LP, Innate Pharma SA, Macrophage Pharma Ltd, MorphoSys AG, Mosaic Biomedicals SL, Norgine Pharmaceuticals Ltd, Ona Therapeutics SL, Orion Clinical Services Ltd, Piqur Therapeutics AG, PTEN Research Foundation, SFL Services GmbH, T3 Pharmaceuticals AG, UCB Biopharma SPRL, and the Wellcome Trust Ltd. She is on the advisory board for SFL Services GmbH and owns shares in GlaxoSmithKline. E.R. is an employee of, and holds shares in, F. Hoffmann-La Roche Ltd. M.Pr.’s institution received funding from F. Hoffmann-La Roche Ltd with respect to the APHINITY study. A.S. reports a consulting/advisory role with Eli Lilly, Pfizer, and Novartis; travel/accommodations/expenses from Neopharm and Celgene; and has been on speaker bureaus for Teva, F. Hoffmann-La Roche Ltd, and Pfizer (all unrelated to the APHINITY study). D.F.’s and A.A.’s institution has received research funding to support the conduct of APHINITY from F. Hoffmann-La Roche Ltd/Genentech, Inc.; and research funding from AstraZeneca, Tesaro, Novartis, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., and Servier, outside the submitted work. D.P. is a member of the APHINITY Joint Study Management Team and has never received any personal fees for the APHINITY study or outside of the APHINITY study from F. Hoffmann-La Roche Ltd. His institution, Institut Jules Bordet, has received both financial and non-financial (e.g., provision of drugs for study) support for the conduct of the APHINITY study. Institut Jules Bordet has received and still receives research grants or non-financial support outside of APHINITY from F. Hoffmann-La Roche Ltd. J.Ba. was an employee of AstraZeneca, served on the Board of Directors of Foghorn, and was a past board member of Varian Medical Systems, Bristol-Myers Squibb, Grail, Aura Biosciences, and Infinity Pharmaceuticals. He had performed consulting and/or advisory work for Grail, PMV Pharma, ApoGen, Juno, Lilly, Seragon, Novartis, and Northern Biologics. He had stock or other ownership interests in PMV Pharma, Grail, Juno, Varian, Foghorn, Aura, Infinity, and ApoGen, as well as Tango and Venthera, for which he is a co-founder. He had previously received honoraria or travel expenses from F. Hoffmann-La Roche Ltd, Novartis, and Lilly. He had also received from F. Hoffmann-La Roche Ltd non-financial support for studies’ drug supplies and conduct. G.V. has received travel grants and remuneration for advisory board meetings from F. Hoffmann-La Roche Ltd. His institution received investigators’ fees for the APHINITY study. L.L.R. has received airfare, taxi fare, and accommodation payments to attend APHINITY Steering Committee meetings since 2012. E.F. has received <$500 airfare and accommodation payments to attend APHINITY Steering Committee meetings. R.D.G.’s institution receives support for his salary from F. Hoffmann-La Roche Ltd, Pfizer, AstraZeneca, Merck, Ipsen, Ferring, Celgene, and Novartis. He has received travel support payments to attend APHINITY Steering Committee meetings from F. Hoffmann-La Roche Ltd. M.Pi. serves on the Scientific Board for Oncolytic. She has received honoraria for consulting roles for AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Inc., Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Periphagen, Pfizer, F. Hoffmann-La Roche Ltd, and Seattle Genetics, and her institute has received research grants from AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, F. Hoffmann-La Roche Ltd/Genentech, Inc., Servier, and Synthon. C.J. has received travel support payments for Steering Committee meetings, consulting fees, and honoraria from F. Hoffmann-La Roche Ltd for the APHINITY study. His institution received investigators’ fees for the APHINITY study. J.A.P. is an employee of Genentech, Inc. and has shares in F. Hoffmann-La Roche Ltd.

Figures

Fig. 1. Mean EORTC QLQ-C30 global health status scores in patients in the pertuzumab plus trastuzumab and chemotherapy arm (solid line) or the placebo plus trastuzumab and chemotherapy arm (dashed line).

Analysis is by ITT population. Higher scores indicate better health status. Horizontal lines indicate the level at which the change from baseline was considered clinically meaningful, with asterisks indicating time points where there was a clinically meaningful change. The lines are slightly offset to improve visibility, but time points are the same for each arm. aFor patients receiving anthracycline-based chemotherapy, the actual time point was week 10 or week 13 of HER2-targeted treatment (depending on the chemotherapy regimen given). For patients receiving non-anthracycline-based chemotherapy (i.e., the pertuzumab plus trastuzumab and docetaxel–carboplatin regimen), this was week 19 of HER2-targeted treatment. EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core module, version 3; FU follow-up; mo months. From The New England Journal of Medicine, von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, and Baselga J, for the APHINITY Steering Committee and Investigators, Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer, 377, 122–131. Copyright © (2017) Massachusetts Medical Society. Adapted with permission.

Fig. 2. Mean EORTC QLQ-C30 scores for functioning scales in patients in the pertuzumab plus trastuzumab and chemotherapy arm (solid line) or the placebo plus trastuzumab and chemotherapy arm (dashed line).

a Physical functioning. b Role functioning. Higher scores indicate better health status. Horizontal lines indicate the level at which the change from baseline was considered clinically meaningful, with asterisks indicating time points where there was a clinically meaningful change. The lines are slightly offset to improve visibility, but time points are the same for each arm. The numbers below graphs indicate the number of patients who completed the scale. aFor patients receiving anthracycline-based chemotherapy, the actual time point was week 10 or week 13 of HER2-targeted treatment (depending on the chemotherapy regimen given). For patients receiving non-anthracycline-based chemotherapy (i.e., the pertuzumab plus trastuzumab and docetaxel–carboplatin regimen), this was week 19 of HER2-targeted treatment. EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core module, version 3, FU follow-up, mo months.

Fig. 3. Mean EORTC QLQ-C30 scores for the diarrhoea symptom scale in patients in the pertuzumab plus trastuzumab and chemotherapy arm (solid line) or the placebo plus trastuzumab and chemotherapy arm (dashed line).

Numbers below graphs indicate the number of patients who completed the scale. Higher scores indicate worse/deteriorating symptoms. Horizontal lines indicate the level at which the change from baseline was considered clinically meaningful, with asterisks indicating time points where there was a clinically meaningful change. The lines are slightly offset to improve visibility, but time points are the same for each arm. aFor patients receiving anthracycline-based chemotherapy, the actual time point was week 10 or week 13 of HER2-targeted treatment (depending on the chemotherapy regimen given). For patients receiving non-anthracycline-based chemotherapy (i.e., the pertuzumab plus trastuzumab and docetaxel–carboplatin regimen), this was week 19 of HER2-targeted treatment. EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core module, version 3, FU follow-up, mo months.

Fig. 4. Mean EORTC QLQ-C30 scores for symptom scales in patients in the pertuzumab plus trastuzumab and chemotherapy arm (solid line) or the placebo plus trastuzumab and chemotherapy arm (dashed line).

a Fatigue. b Dyspnoea. c Appetite loss. The numbers below the graphs indicate the number of patients who completed the scale. Higher scores indicate worse/deteriorating symptoms. Horizontal lines indicate the level at which the change from baseline was considered clinically meaningful, with asterisks indicating time points where there was a clinically meaningful change. The lines are slightly offset to improve visibility, but time points are the same for each arm. aFor patients receiving anthracycline-based chemotherapy, the actual time point was week 10 or week 13 of HER2-targeted treatment (depending on the chemotherapy regimen given). For patients receiving non-anthracycline-based chemotherapy (i.e., the pertuzumab plus trastuzumab and docetaxel–carboplatin regimen), this was week 19 of HER2-targeted treatment. EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core module, version 3, FU follow-up, mo months.

Fig. 5. EORTC QLQ-BR23 scores (change from baseline) for symptom scales in patients in the pertuzumab plus trastuzumab and chemotherapy arm (solid line) or the placebo plus trastuzumab and chemotherapy arm (dashed line).

a Systemic therapy side effects. b Future perspectives. Values outside the shaded area represent clinically meaningful changes, with asterisks indicating time points where there was a clinically meaningful change. Numbers below the graphs represent patients completing the response at each time point. Higher scores indicate improved future perspectives; higher scores indicate worsening in symptoms of systemic therapy side effects. The lines are slightly offset to improve visibility, but time points are the same for each arm. aFor patients receiving anthracycline-based chemotherapy, the actual time point was week 10 or week 13 of HER2-targeted treatment (depending on the chemotherapy regimen given). For patients receiving non-anthracycline-based chemotherapy (i.e., the pertuzumab plus trastuzumab and docetaxel–carboplatin regimen), this was week 19 of HER2-targeted treatment. EORTC QLQ-BR23 European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Breast module, FU follow-up, mo months.