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Addition of Alpelisib to Fulvestrant for PIK3CA-Mutant, HR-Positive, HER2-Negative Advanced Breast Cancer: Patient-Reported Outcomes


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In an analysis from the PIK3CA-mutant cohort of the phase III SOLAR-1 trial reported in the Journal of Clinical Oncology, Eva Ciruelos, MD, PhD, and colleagues found that the addition of alpelisib to fulvestrant was not associated with significant worsening of global health status/quality of life but was associated with worse outcomes on symptom subscales in patients with advanced hormone receptor (HR)-positive, HER2-negative advanced breast cancer.  

Eva Ciruelos, MD, PhD

Eva Ciruelos, MD, PhD

In the trial, the addition of the PI3Kα-selective inhibitor alpelisib to fulvestrant significantly improved progression-free survival vs placebo plus fulvestrant among patients with PIK3CA-mutant disease but did not meet the primary efficacy objective among patients without a PIK3CA mutation. The current health-related quality-of-life analysis based on patient-reported outcomes was thus conducted only in the PIK3CA-mutant cohort.

Study Details

In the PIK3CA-mutant cohort, 341 patients were randomly assigned to receive alpelisib at 300 mg daily (n = 162) or placebo (n = 172) plus fulvestrant at 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 EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), with the global health status/quality of life (GHS/QOL) score being the main variable of interest, as well as the Brief Pain Inventory-Short Form (BPI).

Key Findings

GHS/QOL and QLQ-C30 functional subscale status were maintained from baseline through 96 weeks (mean changes < 10 points) in both the alpelisib and placebo groups.

In SOLAR-1, there was no statistical difference in deterioration of GHS/QOL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib.
— Eva Ciruelos, MD, PhD, and colleagues

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Concerning the GHS/QOL score, the overall change from baseline was -3.50 points (95% confidence interval [CI] = -8.02 to 1.02 points) in the alpelisib group vs 0.27 (95% CI = -4.48 to 5.02) in the placebo group. The overall treatment effect did not significantly differ between groups (-3.77, 95% CI = -8.35 to 0.80, P = .101). Adjusted mean changes from baseline were within 5 points for all visits in both groups, with a mean between-treatment difference of < 3 points at all visits. Time to 10% deterioration on the GHS/QOL did not differ between groups (hazard ratio = 1.03, 95% CI = 0.72–1.48).

No significant differences between groups were observed in the functional subscales for physical, emotional, role, or cognitive function through 96 weeks. A poorer outcome in social functioning was observed in the alpelisib group (treatment difference = -4.98, 95% CI = -8.86 to -1.09, P = .012).

On the QLQ-C30 symptom subscales, the alpelisib group had worse mean changes from baseline on scores for appetite loss (10.96 vs 1.83, P < .001), diarrhea (13.39 vs 1.63, P < .001), nausea or vomiting (6.97 vs 4.14, P = .019), and fatigue (9.85 vs 3.34, P =.014), but improved outcomes in constipation (-8.54 vs -3.61, P = .004).

On the BPI, the alpelisib group had higher numeric improvement (42% vs 32%) and lower numeric worsening (24% v 35%) in worst pain at week 24 (P = .090).

The investigators concluded, “In SOLAR-1, there was no statistical difference in deterioration of GHS/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 HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer.”

Fabrice André, MD, of the Department of Medical Oncology, Institut Gustave Roussy, Villejuif, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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