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. 2021 Jun 20;39(18):2005-2015.
doi: 10.1200/JCO.20.01139. Epub 2021 Mar 29.

Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1

Eva Maria Ciruelos  1 , Hope S Rugo  2 , Ingrid A Mayer  3 , Christelle Levy  4 , Frédéric Forget  5 , Juan Ignacio Delgado Mingorance  6 , Tamar Safra  7 , Norikazu Masuda  8 , Yeon Hee Park  9 , Dejan Juric  10 , Pierfranco Conte  11 , Mario Campone  12 , Sibylle Loibl  13   14 , Hiroji Iwata  15 , Xiaolei Zhou  16 , Jinhee Park  17 , Antonia Ridolfi  18 , Ines Lorenzo  19 , Fabrice André  20
Affiliations

Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1

Eva Maria Ciruelos et al. J Clin Oncol. .

Abstract

Purpose: In the phase III SOLAR-1 trial (NCT02437318), the PI3Kα-selective inhibitor and degrader alpelisib significantly improved median progression-free survival when added to fulvestrant in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed health-related quality of life using patient-reported outcome measures in these patients.

Materials and methods: In the PIK3CA-mutant cohort, 341 patients were randomly assigned 1:1 to receive alpelisib 300 mg daily or placebo plus fulvestrant 500 mg on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Patient-reported outcomes were evaluated with the European Organisation for Research and Treatment of Cancer QoL of Cancer Patients and Brief Pain Inventory-Short Form questionnaires. Changes from baseline and time to 10% deterioration were analyzed using repeated measurement models and Cox models, respectively.

Results: Global Health Status/QoL and functional status were maintained from baseline (mean changes < 10 points) in the alpelisib (overall change from baseline [95% CI], -3.50 [-8.02 to 1.02]) and placebo arms (overall change from baseline [95% CI], 0.27 [-4.48 to 5.02]). Overall treatment effect in Global Health Status/QoL was not significantly different between arms (-3.77; 95% CI, -8.35 to 0.80; P = .101). Time to 10% deterioration for Global Health Status/QoL was similar between arms (hazard ratio, 1.03; 95% CI, 0.72 to 1.48). Compared with placebo, deterioration in social functioning and in diarrhea, appetite loss, nausea or vomiting, and fatigue symptom subscales occurred with alpelisib. Numerical improvement in Worst Pain was observed with alpelisib versus placebo (42% v 32%, week 24; P = .090).

Conclusion: In SOLAR-1, there was no statistical difference in deterioration of Global Health Status/QoL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. Treatment decisions must consider efficacy and tolerability; taken with clinical efficacy, these results support the benefit-risk profile of alpelisib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative PIK3CA-mutated advanced breast cancer.

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Conflict of interest statement

Eva Maria CiruelosConsulting or Advisory Role: Roche, Pfizer, AstraZeneca, Novartis, LillySpeakers' Bureau: Lilly, Roche, PfizerTravel, Accommodations, Expenses: Roche, Pfizer Hope S. RugoConsulting or Advisory Role: Samsung, Celltrion, Puma BiotechnologyResearch Funding: Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, Genentech, Merck, Immunomedics, Odonate Therapeutics, Daiichi Sankyo, Seattle GeneticsTravel, Accommodations, Expenses: Pfizer, Novartis, Macrogenics, Mylan, Daiichi Sankyo, AstraZeneca SpainOpen Payments Link: https://openpaymentsdata.cms.gov/summary Ingrid A. MayerConsulting or Advisory Role: Novartis, AstraZeneca, Lilly, Genentech, GlaxoSmithKline, Immunomedics, Macrogenics, Pfizer, Abbvie, Seattle Genetics, Puma Biotechnology, Cyclacel, Blueprint MedicinesResearch Funding: Novartis, Pfizer, Genentech Frederic ForgetTravel, Accommodations, Expenses: Ipsen, Teva Norikazu MasudaLeadership: Japan Breast Cancer Research Group, Japan Breast Cancer Society (JBCS)Honoraria: Chugai Pharma, AstraZeneca, Pfizer, Eisai, Lilly Japan, Takeda, Kyowa Hakko Kirin, Novartis, Daiichi SankyoResearch Funding: Chugai Pharma, AstraZeneca, Kyowa Hakko Kirin, MSD, Novartis, Pfizer, Lilly, Eisai, Daiichi Sankyo, Nihonkayaku Yeon Hee ParkHonoraria: Novartis, Pfizer, MerckConsulting or Advisory Role: Pfizer, Roche, Eisai, Daiichi-Sankyo, AstraZenecaResearch Funding: AstraZeneca, Pfizer, Novartis, MerckTravel, Accommodations, Expenses: Merck, Novartis Dejan JuricConsulting or Advisory Role: Novartis, EMD Serono, Eisai, Genentech, Ipsen, Syros Pharmaceuticals, MapKure, Vibliome Therapeutics, Petra PharmaResearch Funding: Novartis, Genentech, Takeda, Eisai, EMD Serono, Placon, Amgen, Syros Pharmaceuticals, InventisBio, Infinity Pharmaceuticals, Takeda, Pfizer Pier ConteSpeakers' Bureau: Roche/Genentech, Novartis, AstraZeneca, Lilly, Tesaro, Bristol-Myers SquibbResearch Funding: Roche, Novartis, Merck KGaA, Bristol-Myers SquibbTravel, Accommodations, Expenses: Novartis, Celgene, AstraZeneca, Pfizer Mario CamponeHonoraria: Novartis, Lilly, GT1Consulting or Advisory Role: Novartis, SERVIER, Menarini, Sanofi, Lilly, Pfizer, AstraZeneca/MedImmune, Abbvie, Pierre Fabre, Accord Healthcare, Sandoz-Novartis, Seattle Genetics, Daiichi Sankyo Europe GmbHSpeakers' Bureau: Novartis, AmgenResearch Funding: NovartisTravel, Accommodations, Expenses: Novartis, AstraZeneca, PfizerOther Relationship: Roche Sibylle LoiblHonoraria: Chugai PharmaConsulting or Advisory Role: Pfizer, Roche, Novartis, Seattle Genetics, Celgene, Lilly, AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck KGaA, Abbvie, Amgen, prime/Medscape, Daiichi Sankyo, Samsung, Puma Biotechnology, Pierre Fabre, Immunomedics, GlaxoSmithKline, EirGenix, BayerResearch Funding: Abbvie, AstraZeneca, Vifor Pharma, Amgen, Celgene, Novartis, Pfizer, Roche, Myriad Genetics, Immunomedics, Seattle Genetics, Daiichi Sankyo, Pierre FabrePatents, Royalties, Other Intellectual Property: Patent Pending EP14153692.0 Hiroji IwataHonoraria: Chugai Pharma, AstraZeneca, Eisai, Pfizer, Daiichi Sankyo, Lilly Japan, Novartis, Kyowa Hakko KirinConsulting or Advisory Role: Chugai Pharma, Daiichi Sankyo, Pfizer, AstraZeneca, Lilly Japan, Kyowa Hakko Kirin, NovartisResearch Funding: MSD, AstraZeneca, Eisai, Kyowa Hakko Kirin, GlaxoSmithKline, Daiichi Sankyo, Chugai Pharma, Nihonkayaku, Lilly Japan, Novartis, Bayer, Pfizer Xiaolei ZhouStock and Other Ownership Interests: Acadia, MerckResearch Funding: Novartis, ADC Therapeutics, Abbvie, EMD Serono/Merck, Otsuka, Bayer, Roche Jinhee ParkEmployment: NovartisStock and Other Ownership Interests: Novartis Antonia RidolfiEmployment: Novartis Ines LorenzoEmployment: NovartisStock and Other Ownership Interests: NovartisHonoraria: Novartis Fabrice AndréResearch Funding: AstraZeneca, Novartis, Pfizer, Lilly, Roche, Daiichi SankyoTravel, Accommodations, Expenses: Novartis, Roche, GlaxoSmithKline, AstraZenecaNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
(A) Changes from baseline in EORTC QLQ-C30 Global Health Status/QoL scale score and (B) overall mean change from baseline in EORTC QLQ-C30 functioning subscale scores, PIK3CA-mutant cohort. In (A), error bars for mean baseline scores indicate ± SD; error bars for LS means for change from baseline indicate ± SEM. Changes from baseline over time were estimated from a repeated measurement model that included terms for treatment, stratification factors, time, treatment-by-time interaction, and baseline score; to ensure the model provided stable estimates, data were cut when patient numbers were < 10 in each treatment arm. Overall mean changes from baseline scores were estimated using repeated measurement models that included terms for treatment, stratification factors, time, and baseline score. The treatment-by-time interaction term was tested, and none was significant. This analysis only included assessments up to the time point at which there were at least 10 patients in each of the treatment groups. Changes > 0 indicate improvement from baseline. In (B), error bars indicate 95% CIs; aindicates P < .05 for treatment difference. EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients questionnaire; LS, least squares; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; QoL, quality of life; W, week.
FIG 2.
FIG 2.
Time to 10% deterioration in European Organisation for Research and Treatment of Cancer Global Health Status/quality of life scale score, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha–mutant cohort. Data include all randomly assigned patients in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha–mutant cohort. mPFS, median progression-free survival.
FIG 3.
FIG 3.
TTD in European Organisation for Research and Treatment of Cancer functioning subscale scores, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha–mutant cohort. HR, hazard ratio; TTD, time to 10% deterioration.
FIG 4.
FIG 4.
(A) Estimated overall mean changes from baselinea and (B) treatment effect in European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients symptom scores, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha–mutant cohort. This analysis only included assessments up to the time point at which there were at least 10 patients in each of the treatment arms. All the time-by-treatment interaction was > 0.05; the overall treatment effects were estimated using the repeated measurements models that included terms for treatment, stratification factors, time, and baseline score, with bars indicating 95% CIs. aOverall mean changes from baseline scores were estimated using repeated measurement models that included terms for treatment, stratification factors, time, and baseline score; changes < 0 indicate improvement from baseline, with bars indicating 95% CIs. LS, least squares.
FIG 5.
FIG 5.
Changes from baseline in (A) BPI-SF Worst Pain and (B) Pain Severity Index, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha–mutant cohort. (A) and (B) The time profile provides the average estimates for the change from baseline for the interval from baseline up to the respective cycle as derived from the repeated measurement model. The mixed-effect model includes terms for treatment, stratification factors, baseline value, time, and time × treatment interaction. This analysis only includes assessments up to the time point at which there were at least 10 patients in each of the treatment arms. Changes from postbaseline could not be calculated for all patients. BPI-SF, Brief Pain Inventory Short Form; LS, least squares; W, week.
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