CAPItello-291: Capivasertib–Fulvestrant in HR-Positive, HER2-Negative Advanced Breast Cancer

Co-primary 1 (PFS, overall population): 7.2 vs 3.6 months — HR 0.60 (95% CI 0.51–0.71; P<0.001) Co-primary 2 (PFS, AKT pathway–altered population): 7.3 vs 3.1 months — HR 0.50 (95% CI 0.38–0.65; P<0.001) Key secondary (OS, overall population): 18-month OS 73.9% vs 65.0% — HR 0.74 (95% CI 0.56–0.98) Safety signal: Rash (grade ≥3: 12.1%), diarrhea (grade 3: 9.3%), hyperglycemia (any grade: 16.3%)

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Clinical Bottom Line

Adding capivasertib to fulvestrant significantly improved progression-free survival compared with fulvestrant alone in patients with hormone receptor–positive, HER2-negative advanced breast cancer who had progressed on prior aromatase inhibitor therapy. Both co-primary endpoints were met: the benefit was demonstrated in the overall population and was even more pronounced in patients whose tumors harbored AKT pathway alterations. Importantly, approximately two-thirds of enrolled patients had previously received a CDK4/6 inhibitor, making these results directly relevant to the most common clinical scenario oncologists face today in this disease.

This trial positioned capivasertib–fulvestrant as a new treatment option in the post–CDK4/6 inhibitor setting for HR-positive advanced breast cancer. Capivasertib received FDA approval in combination with fulvestrant in late 2023 for this indication, creating a new AKT inhibitor–based option alongside existing choices such as alpelisib–fulvestrant (for PIK3CA-mutated tumors) and elacestrant (for ESR1-mutated tumors). The observation that capivasertib produced benefit across both pathway-altered and the broader unselected population adds clinical flexibility, though the magnitude of benefit was numerically greater in the AKT pathway–altered subgroup.

The toxicity profile of capivasertib requires active management. Diarrhea, rash, and hyperglycemia are the signature adverse effects, with rash and diarrhea each reaching grade 3 or higher in a meaningful proportion of patients. The intermittent dosing schedule (4 days on, 3 days off) was designed to mitigate toxicity, but dose interruptions were still required in over a third of patients. Clinicians should be prepared for proactive monitoring and management of these class-effect toxicities from the outset.

Trial Overview

Study Design

• Trial name and registration: CAPItello-291 (NCT04305496)
• Design: Phase 3, randomized, double-blind, placebo-controlled, prespecified interim analysis
• Randomization: 1:1 ratio, stratified by presence or absence of liver metastases, previous use of a CDK4/6 inhibitor (yes or no), and geographic region
• Setting: HR-positive, HER2-negative locally advanced (primary inoperable) or metastatic breast cancer; relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous CDK4/6 inhibitor therapy
• Enrollment period and sites: June 2, 2020, to October 13, 2021, at 193 centers in 19 countries (181 sites contributed randomized patients)

This trial used dual co-primary endpoints: investigator-assessed PFS in the overall population and in the AKT pathway–altered population. AKT pathway alteration status was determined centrally by next-generation sequencing (FoundationOne CDx or OncoScreen Plus in China) after randomization and was not used as a stratification factor. A minimum of 51% of patients with previous CDK4/6 inhibitor treatment was required per protocol. Overall survival was assessed at the primary PFS analysis as a no-detriment analysis with a 0.01% alpha penalty.

Mechanism of Action

Capivasertib is a highly selective, potent inhibitor of all three isoforms of the serine/threonine kinase AKT (AKT1, AKT2, AKT3). The PI3K/AKT/PTEN pathway is one of the most commonly activated signaling cascades in HR-positive breast cancer and is a key mediator of endocrine therapy resistance. Activating mutations in PIK3CA, AKT1, or loss-of-function alterations in PTEN lead to constitutive AKT signaling, promoting tumor cell survival and proliferation. Capivasertib directly inhibits AKT kinase activity, thereby blocking downstream signaling through mTOR and other effectors. By combining AKT inhibition with the estrogen receptor degrader fulvestrant, the regimen targets both endocrine resistance mechanisms and estrogen-dependent tumor growth [2].

Patient Population

• Key eligibility: Pre-, peri-, or postmenopausal women and men (≥18 years; ≥20 in Japan) with HR-positive, HER2-negative locally advanced or metastatic breast cancer; disease progression during previous aromatase inhibitor therapy with or without CDK4/6 inhibitor; up to two previous lines of endocrine therapy and one previous line of chemotherapy for advanced disease; ECOG PS 0 or 1; measurable disease per RECIST v1.1 or assessable bone lesion.
• Key exclusions: Previous fulvestrant, SERD, AKT/PI3K/mTOR inhibitors, or insulin-treated diabetes with HbA1c ≥8.0%.
• Biomarker selection: AKT pathway–altered tumors (PIK3CA, AKT1, or PTEN alterations) identified centrally by next-generation sequencing after randomization; dual primary endpoint tested in both overall population and AKT pathway–altered population.
• Sample size flow: 901 patients enrolled → 708 randomized (355 capivasertib–fulvestrant, 353 placebo–fulvestrant) → 705 treated (safety population: 355 capivasertib–fulvestrant, 350 placebo–fulvestrant) → 708 analyzed for efficacy (ITT). Among the 708 randomized patients, 289 (40.8%) had AKT pathway–altered tumors, 313 (44.2%) had confirmed AKT pathway–nonaltered tumors, and 106 (15.0%) had unknown alteration status.

Baseline Characteristics

Baseline characteristics were generally well balanced between arms. Approximately 69% of patients had received prior CDK4/6 inhibitor therapy for advanced disease, and roughly 18% had received prior chemotherapy in the advanced setting. Over one-third of patients had primary endocrine resistance.

Treatment Protocol

Experimental Arm: Capivasertib–Fulvestrant (n=355 randomized; safety population n=355)

Oral capivasertib plus intramuscular fulvestrant. Premenopausal or perimenopausal women also received a luteinizing hormone–releasing hormone agonist.

• Dose and schedule: Capivasertib 400 mg twice daily for 4 days, followed by 3 days off (one cycle = 4 weeks); fulvestrant 500 mg intramuscularly every 14 days for the first three injections and every 28 days thereafter
• Treatment duration: Until disease progression, unacceptable toxic effects, withdrawal of consent, or death
• Median treatment duration: 5.4 months (capivasertib); 5.8 months (fulvestrant)
• Median relative dose intensity: Not reported in this publication

At the data cutoff, 63 patients (17.7%) were continuing to receive treatment with capivasertib. Capivasertib was discontinued in 292 patients (82.3%), most commonly due to disease progression in 209 patients (58.9%).

Control Arm: Placebo–Fulvestrant (n=353 randomized; safety population n=350)

Matching oral placebo plus intramuscular fulvestrant. Premenopausal or perimenopausal women also received a luteinizing hormone–releasing hormone agonist.

• Dose and schedule: Matching placebo for 4 days on/3 days off; fulvestrant 500 mg intramuscularly every 14 days for the first three injections and every 28 days thereafter
• Treatment duration: Until disease progression, unacceptable toxic effects, withdrawal of consent, or death
• Median treatment duration: 3.6 months (placebo); 3.7 months (fulvestrant)

At the data cutoff, 43 patients (12.3%) were continuing to receive placebo. Placebo was discontinued in 307 patients (87.7%), most commonly due to disease progression in 273 patients (78.0%).

Efficacy Outcomes

Co-Primary Endpoint 1: Investigator-Assessed Progression-Free Survival — Overall Population

Definition: Investigator-assessed progression-free survival assessed according to RECIST, version 1.1, in the overall population

Analysis population: All patients who underwent randomization (overall population, N=708)

Alpha allocation: Two-sided P<0.035 (with recycling of remaining 1.5% alpha from co-primary endpoint 2)

Statistical method: Log-rank test stratified by presence or absence of liver metastases, previous use of a CDK4/6 inhibitor, and geographic area; hazard ratio from stratified Cox proportional-hazards model with Efron method

Median follow-up: 13.0 months (range, 0.0 to 25.0) in the capivasertib–fulvestrant group and 12.7 months (range, 0.0 to 22.3) in the placebo–fulvestrant group

Capivasertib–Fulvestrant: 7.2 months (95% CI, 5.5 to 7.4); 258 events in 355 patients Placebo–Fulvestrant: 3.6 months (95% CI, 2.8 to 3.7); 293 events in 353 patients Comparison: HR 0.60 (95% CI, 0.51 to 0.71; P<0.001)

The primary analysis was conducted after the occurrence of 551 events of disease progression or death (planned: 542 events).

Co-Primary Endpoint 2: Investigator-Assessed Progression-Free Survival — AKT Pathway–Altered Population

Definition: Investigator-assessed progression-free survival assessed according to RECIST, version 1.1, among patients with AKT pathway–altered (PIK3CA, AKT1, or PTEN) tumors

Analysis population: Patients with AKT pathway–altered tumors (N=289: 155 capivasertib–fulvestrant, 134 placebo–fulvestrant)

Alpha allocation: Two-sided P<0.05 (with recycling of remaining 1.5% alpha from overall population)

Statistical method: Log-rank test stratified by presence or absence of liver metastases and previous use of a CDK4/6 inhibitor; hazard ratio from stratified Cox proportional-hazards model with Efron method

Capivasertib–Fulvestrant: 7.3 months (95% CI, 5.5 to 9.0); 121 events in 155 patients Placebo–Fulvestrant: 3.1 months (95% CI, 2.0 to 3.7); 115 events in 134 patients Comparison: HR 0.50 (95% CI, 0.38 to 0.65; P<0.001)

At the primary analysis, 236 events of progression or death had occurred in the AKT pathway–altered population (planned: 217 events).

Multiplicity Control

Alpha was split between two co-primary populations: the overall population was tested at a two-sided significance level of 0.035, and the AKT pathway–altered population was tested at a two-sided significance level of 0.05, with recycling of the remaining 1.5% alpha. Both co-primary endpoints were met, with P<0.001 in both populations. Overall survival assessments at the primary PFS analysis carried a 0.01% alpha penalty as a no-detriment evaluation.

Key Secondary Endpoints

Overall Survival — Overall Population

This endpoint was not formally tested at this analysis. A formal analysis of overall survival had not been triggered — a sufficient number of deaths had not occurred by the data-cutoff date. The OS data presented represent a descriptive, immature analysis.

Analysis population: All patients who underwent randomization (overall population, N=708)

At the time of analysis, 195 patients (27.5%) had died: 87 in the capivasertib–fulvestrant group and 108 in the placebo–fulvestrant group.

18-month OS rate:

• Capivasertib–Fulvestrant: 73.9% (95% CI, 68.3 to 78.7)
• Placebo–Fulvestrant: 65.0% (95% CI, 58.7 to 70.6)
• HR 0.74 (95% CI, 0.56 to 0.98)

This endpoint was not formally tested in the statistical hierarchy. The result should be interpreted as descriptive.

Overall Survival — AKT Pathway–Altered Population

This endpoint was not formally tested at this analysis.

Analysis population: Patients with AKT pathway–altered tumors (N=289)

• Deaths: 41 in the capivasertib–fulvestrant group and 46 in the placebo–fulvestrant group

18-month OS rate:

• Capivasertib–Fulvestrant: 73.2% (95% CI, 64.8 to 80.0)
• Placebo–Fulvestrant: 62.9% (95% CI, 53.1 to 71.2)
• HR 0.69 (95% CI, 0.45 to 1.05)

This endpoint was not formally tested in the statistical hierarchy. The result should be interpreted as descriptive.

Objective Response

Objective response rate data were reported in the Supplementary Appendix (Table S3) but are not reported in the main publication text.

BICR-Assessed PFS

Blinded independent central review–assessed PFS was consistent with investigator-assessed analyses: - Overall population: HR 0.61 (95% CI, 0.50 to 0.73) - AKT pathway–altered population: HR 0.51 (95% CI, 0.38 to 0.68)

These endpoints were not formally tested in the statistical hierarchy.

Quality of Life — Time to Deterioration (QLQ-C30)

Analysis population: Overall population

The median time to deterioration (defined as a sustained decrease of ≥10 points in the QLQ-C30 global health status/quality of life score from baseline) was 24.9 months in the capivasertib–fulvestrant group, as compared with 12.0 months in the placebo–fulvestrant group (HR 0.70; 95% CI, 0.53 to 0.92). This endpoint was not formally tested in the statistical hierarchy.

The mean overall change from baseline in the QLQ-C30 score at visits during the treatment period was −2.52 points in the capivasertib–fulvestrant group and −5.62 points in the placebo–fulvestrant group (difference, 3.10 points; 95% CI, 0.21 to 5.98).

Exploratory Endpoints

Efficacy by AKT Pathway Alteration Status

PFS benefit with capivasertib–fulvestrant was observed across biomarker-defined populations, though the magnitude varied:

• AKT pathway–altered (N=289): HR 0.50 (95% CI, 0.38 to 0.65) — co-primary endpoint, formally tested
• AKT pathway–nonaltered including unknown NGS results (N=419): HR 0.70 (95% CI, 0.56 to 0.88)
• AKT pathway–nonaltered excluding unknown NGS results (N=313): HR 0.79 (95% CI, 0.61 to 1.02)
• Unknown NGS result (N=106): HR 0.52 (95% CI, 0.32 to 0.83) — post hoc analysis

These exploratory and post hoc analyses were not formally tested. Notably, the confidence interval for PFS in the confirmed AKT pathway–nonaltered population (excluding unknown results) crossed 1.0, suggesting that the benefit of capivasertib may be attenuated in patients without pathway alterations, though this comparison is exploratory and hypothesis-generating.

Safety

Safety Population

The safety population included 355 patients who received capivasertib–fulvestrant and 350 who received placebo–fulvestrant.

Safety Summary

Grade 3 and Grade 4 Adverse Events of Clinical Significance

The source publication reported grade 3 and grade 4 events separately in Table 2. The most clinically significant grade 3 or higher adverse events are presented below.

The most common any-grade adverse events with capivasertib–fulvestrant included diarrhea (257 [72.4%] vs 70 [20.0%]), rash as a grouped term (135 [38.0%] vs 25 [7.1%]), nausea (123 [34.6%] vs 54 [15.4%]), fatigue (74 [20.8%] vs 45 [12.9%]), vomiting (73 [20.6%] vs 17 [4.9%]), and hyperglycemia (58 [16.3%] vs 13 [3.7%]). Rash is reported as a grouped term including the preferred terms of rash, rash macular, maculopapular rash, rash papular, and rash pruritic.

Adverse Events of Special Interest

⚠️ Rash: Critical Safety Signal

• Any grade: 135 (38.0%) capivasertib–fulvestrant vs 25 (7.1%) placebo–fulvestrant
• Grade 3: 43 (12.1%) vs 1 (0.3%)
• Clinical implication: Rash was the most frequent grade ≥3 adverse event with capivasertib. It is reported as a grouped term encompassing multiple rash subtypes. Dose interruptions and reductions should follow prescribing information guidance. Dermatologic assessment and early intervention are recommended.

⚠️ Diarrhea: Critical Safety Signal

• Any grade: 257 (72.4%) capivasertib–fulvestrant vs 70 (20.0%) placebo–fulvestrant
• Grade 3: 33 (9.3%) vs 1 (0.3%)
• Clinical implication: Diarrhea occurred in nearly three-quarters of patients receiving capivasertib. Proactive counseling, early antidiarrheal intervention, and monitoring for dehydration are essential from cycle 1.

Hyperglycemia

• Any grade: 58 (16.3%) capivasertib–fulvestrant vs 13 (3.7%) placebo–fulvestrant
• Grade 3: 7 (2.0%) vs 1 (0.3%)
• Grade 4: 1 (0.3%) vs 0
• Clinical implication: Hyperglycemia is a known class effect of AKT inhibitors. Fasting glucose should be monitored regularly. Patients with insulin-treated diabetes and HbA1c ≥8.0% were excluded from the trial. Management should follow prescribing information guidance, and endocrinology consultation may be warranted for persistent or severe hyperglycemia.

Deaths

At the time of analysis, 195 patients (27.5%) had died: 87 in the capivasertib–fulvestrant group and 108 in the placebo–fulvestrant group.

Death due to adverse events occurred in 4 patients (1.1%) receiving capivasertib–fulvestrant (acute myocardial infarction, cerebral hemorrhage, aspiration pneumonia, and sepsis) and in 1 patient receiving placebo–fulvestrant (coronavirus disease 2019). None of the deaths were considered by the local investigators to be related to capivasertib or fulvestrant.

Subgroup Analyses

Subgroup analyses for the co-primary endpoint (investigator-assessed PFS in the overall population) demonstrated a consistent benefit of capivasertib–fulvestrant across prespecified subgroups:

These subgroup analyses were prespecified and were not powered for formal statistical comparisons. Results should be interpreted as hypothesis-generating.

Of note, the subgroup of pre- or perimenopausal women showed a numerically attenuated benefit (HR 0.86; 95% CI, 0.60 to 1.20) compared with postmenopausal women (HR 0.59; 95% CI, 0.48 to 0.71). The confidence interval for the pre-/perimenopausal subgroup crossed 1.0. This difference may reflect biological differences, smaller sample size, or chance, and warrants further investigation. The benefit was consistent regardless of prior CDK4/6 inhibitor use, endocrine resistance pattern, or presence of liver metastases.

Key Comparator Trials

Cross-trial comparisons are limited by differences in patient populations, trial designs, and endpoints. These data are presented for context, not for direct statistical comparison.

Contextual Notes

CAPItello-291 enters a treatment landscape increasingly defined by biomarker-directed therapy after CDK4/6 inhibitor progression. The SOLAR-1 trial established alpelisib–fulvestrant specifically in PIK3CA-mutated tumors [4], but that combination carries a notably challenging safety profile dominated by hyperglycemia and was studied predominantly in patients who had not received prior CDK4/6 inhibitors. CAPItello-291 is differentiated by its broader population (not limited to a single mutation), its high proportion of patients with prior CDK4/6 inhibitor exposure, and its dual primary endpoint design that tested both an all-comer and a biomarker-enriched population.

Elacestrant (EMERALD trial) demonstrated a PFS benefit as monotherapy in the post–CDK4/6 inhibitor setting, including enriched benefit in ESR1-mutated tumors [5]. The absolute PFS gain with elacestrant was more modest. The choice between capivasertib–fulvestrant, alpelisib–fulvestrant, and elacestrant increasingly depends on tumor genomic profiling — specifically PIK3CA, AKT1, PTEN, and ESR1 mutation status — reinforcing the importance of next-generation sequencing at time of progression.

Grey Zones and Unanswered Questions

• The benefit in the confirmed AKT pathway–nonaltered population is uncertain. The exploratory analysis excluding patients with unknown NGS results showed a PFS hazard ratio of 0.79 (95% CI, 0.61 to 1.02), with the confidence interval crossing 1.0. Whether the approved all-comer indication delivers clinically meaningful benefit to patients whose tumors are confirmed to lack PIK3CA, AKT1, and PTEN alterations remains a critical open question.

• Pre- and perimenopausal women showed attenuated benefit. The subgroup analysis showed a hazard ratio of 0.86 (95% CI, 0.60 to 1.20) for pre-/perimenopausal patients compared with 0.59 (95% CI, 0.48 to 0.71) for postmenopausal patients. While this may reflect sample size limitations, it warrants investigation into whether hormonal milieu or LHRH agonist co-treatment modifies capivasertib efficacy.

• Overall survival data are immature. Only 195 deaths (27.5%) had occurred at the time of the primary PFS analysis. Whether the PFS benefit translates into a definitive overall survival advantage — particularly given the availability of effective post-progression therapies — remains to be established. Subsequent therapy rates and crossover data were not reported in this publication.

• Sequencing relative to alpelisib and elacestrant is undefined. For patients with PIK3CA-mutated tumors, no data exist to guide the choice between capivasertib–fulvestrant and alpelisib–fulvestrant, or the optimal order of these agents. Similarly, optimal sequencing with elacestrant in ESR1-mutated tumors is unknown.

• Patients with prior fulvestrant, SERD, or PI3K/AKT/mTOR inhibitor exposure were excluded. As fulvestrant-based combinations become first-line standards, the efficacy of capivasertib in fulvestrant-pretreated patients is unknown. This exclusion limits the applicability of CAPItello-291 results to an increasingly common clinical scenario.

Clinical Implications

Where This Fits in the Treatment Sequence

Capivasertib–fulvestrant is positioned as a treatment option for patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer who have progressed on prior aromatase inhibitor–based therapy, with or without prior CDK4/6 inhibitor exposure. In the current (2026) treatment algorithm, this typically represents a second- or third-line setting. The regimen is applicable to both AKT pathway–altered and unselected populations based on the dual co-primary endpoint design, though the magnitude of benefit appeared greater in the pathway-altered subgroup. Per NCCN guidelines [3], capivasertib–fulvestrant is a recommended option in the post–CDK4/6 inhibitor endocrine-based treatment setting, with genomic testing (PIK3CA/AKT1/PTEN) recommended to guide therapeutic decisions.

Practical Considerations

Capivasertib uses an intermittent dosing schedule (400 mg twice daily, 4 days on/3 days off) designed to mitigate AKT inhibitor class-effect toxicities. Despite this, dose interruptions occurred in 124 patients (34.9%), dose reductions in 70 (19.7%), and discontinuation due to adverse events in 46 (13.0%). The three signature toxicities requiring proactive management are:

1. Diarrhea (any grade 72.4%): Anticipatory counseling and early antidiarrheal intervention from cycle 1
2. Rash (any grade 38.0%; grade ≥3: 12.1%): Dermatologic assessment, topical therapies, and dose modification per label
3. Hyperglycemia (any grade 16.3%): Fasting glucose monitoring at baseline and regularly during treatment; patients with poorly controlled diabetes were excluded from the trial

Unanswered Questions

The two most practice-relevant open questions are (1) whether the benefit in confirmed AKT pathway–nonaltered patients is clinically meaningful — which has direct implications for whether to require genomic testing before prescribing — and (2) whether the immature overall survival signal (HR 0.74; 95% CI, 0.56 to 0.98) will mature into a statistically significant survival advantage.

Post-Progression Options

Subsequent therapy rates were not reported in this publication. Post-progression options in current practice include chemotherapy (taxanes, capecitabine), trastuzumab deruxtecan (for HER2-low tumors), other endocrine-based regimens (if not previously exhausted), or clinical trial enrollment.

Regulatory and Guideline Status

Regulatory

• FDA: Capivasertib (Truqap) was approved in November 2023 in combination with fulvestrant for the treatment of adult patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy [2].
• EMA: Approved in 2024 for a similar indication restricted to patients with AKT pathway alterations.

⚠️ Regulatory status verified as of March 2026. Confirm current approval status and labeled indications before clinical use at FDA.gov.

Guidelines

• NCCN: Capivasertib–fulvestrant is included as a recommended regimen for HR-positive, HER2-negative recurrent or metastatic breast cancer in the post–CDK4/6 inhibitor setting, with recommendation for PIK3CA/AKT1/PTEN testing [3].

Companion Diagnostics

The FDA-approved companion diagnostic for capivasertib is the FoundationOne CDx assay, which detects PIK3CA, AKT1, and PTEN alterations. Note that while the FDA label restricts the approved indication to patients with pathway alterations, the trial demonstrated co-primary endpoint benefit in the overall (unselected) population as well.

About the Author

Andrew Stevenson is the founder and systems architect of kill-cancer.com, a clinical intelligence platform delivering structured, source-traced oncology trial analysis to practicing clinicians. He holds 17 Google technical certifications in data systems, automation, and applied AI — the engineering foundation behind the extraction and verification pipeline that produces every article on this platform. Every number traces directly to its source publication. Zero calculation. Zero editorializing. Zero hallucination.

Five siblings lost to cancer built the urgency. The engineering builds the trust.

📧 andrew@kill-cancer.com 🌐 kill-cancer.com 💬 kill-cancer.com/forum

Disclaimer

This article is intended for healthcare professionals only. It is not medical advice and should not be used as a substitute for professional clinical judgment. Treatment decisions should be made in consultation with qualified healthcare providers based on individual patient circumstances.

All trial data presented in this article are sourced directly from the published clinical trial report and its supplementary materials. Numbers are reproduced exactly as reported; no calculations, derivations, or estimates have been performed.

Trial results are presented as reported in the source publication. Updated data, label changes, or guideline revisions published after the source article may alter clinical applicability.

Comparator trial data presented in Section 8 are sourced from their respective published reports and are provided for contextual purposes only. Cross-trial comparisons have inherent limitations and should not be interpreted as direct statistical comparisons.

References

1. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor–positive advanced breast cancer. N Engl J Med. 2023;388:2058-2070. doi:10.1056/NEJMoa2214131
2. Truqap (capivasertib) prescribing information. U.S. Food and Drug Administration. 2023.
3. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 1.2026. Accessed March 2026.
4. André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940.
5. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, HER2-negative advanced breast cancer: results of the randomized phase III EMERALD trial. J Clin Oncol. 2022;40:3246-3256.