| <50 years | 27 (17.4) | 29 (21.6) | 56 (19.4) |
| ≥50 to <65 years | 83 (53.5) | 60 (44.8) | 143 (49.5) |
| ≥65 to <75 years | 37 (23.9) | 28 (20.9) | 65 (22.5) |
| ≥75 years | 8 (5.2) | 17 (12.7) | 25 (8.7) |
CAPItello-291: a global, phase 3, randomized, double-blind, multicentre, placebo-controlled trial (N=708)1,4†
289 patients (40.8%) in the overall population had tumours with PIK3CA/AKT1/PTEN alterations
* Day 15 is Week 3 Day 1 of Cycle 1.
Stratification factors: Liver metastases, prior CDK4/6i, and region1,4¶
Dual primary endpoints
- Investigator assessed PFS in:
- overall population** and
- subgroup with PIK3CA/AKT1/PTEN-altered tumours
Key secondary endpoints
- OS
- ORR
AI=aromatase inhibitor; BC=breast cancer; ET=endocrine therapy; HbA1c=hemoglobin A1c; IHC=immunohistochemistry; ISH=in situ hybridization; LHRH=luteinizing hormone-releasing hormone; ORR=objective response rate; OS=overall survival; PFS=progression-free survival.
† In CAPItello-291, a total of 708 patients were randomized 1:1 to receive either 400 mg of TRUQAP (n=355) or placebo (n=353) given twice daily for 4 days followed by 3 days off treatment each week of a 28-day treatment cycle. Fulvestrant 500 mg was administered on Cycle 1 Days 1 and 15 and then at Day 1 of a 28-day cycle. In total, 289 patients had tumours with eligible PIK3CA/AKT1/PTEN-alterations.
‡ TRUQAP is not indicated in men.
§ Pre- or peri-menopausal women also received an LHRH agonist for the duration of the study treatment.
¶ Region 1: United States, Canada, Western Europe, Australia, and Israel; Region 2: Latin America, Eastern Europe, and Russia; Region 3: Asia.
** TRUQAP is only indicated for patients with PIK3CA/AKT1/PTEN alterations.
Patients with PIK3CA/AKT1/PTEN-altered tumours (n=289) represented 40.8% of the overall population.1* Among the altered patients, 76% of patients had a gene alteration in PIK3CA, 13% in AKT1 and 17% in PTEN.1
Patient demographics and disease characteristics for patients with PIK3CA/AKT1/PTEN-altered tumours
| Capivasertib + fulvestrant (n=155) | Placebo + fulvestrant (n=134) | Total (n=289) | |
|---|---|---|---|
| Median age, years (range) | 58.0 (36, 84) |
60.0 (34, 90) |
59.0 (34, 90) |
| Male | 2 (1.3) | 0 | 2 (0.7) |
| Female | 153 (98.7) | 134 (100) | 287 (99.3) |
| Black or African American | 2 (1.3) | 1 (0.7) | 3 (1.0) |
| American Indian or Alaska Native | 1 (0.6) | 1 (0.7) | 2 (0.7) |
| Asian | 48 (31.0) | 35 (26.1) | 83 (28.7) |
| White | 75 (48.4) | 76 (56.7) | 151 (52.2) |
| Other | 29 (18.7) | 21 (15.7) | 50 (17.3) |
| (0) Normal activity | 93 (60.0) | 97 (72.4) | 190 (65.7) |
| (1) Restricted activity | 62 (40.0) | 36 (26.9) | 98 (33.9) |
| (2) In bed less than or equal to 50% of the time | 0 | 1 (0.7) | 1 (0.3) |
| Pre-/peri-menopausal | 23 (14.8) | 29 (21.6) | 52 (18.0) |
| Post-menopausal | 130 (83.9) | 105 (78.4) | 235 (81.3) |
| Aromatase inhibitor | 155 (100) | 134 (100) | 289 (100) |
| Tamoxifen | 69 (44.5) | 57 (42.5) | 126 (43.6) |
| TRUQAP + fulvestrant: studied in a majority CDK4/6i-exposed population1,4* | |||
| Aromatase inhibitor | 155 (100) | 134 (100) | 289 (100) |
| Tamoxifen | 69 (44.5) | 57 (42.5) | 126 (43.6) |
| (Neo)adjuvant treatment only | 62 (40.0) | 61 (45.5) | 123 (42.6) |
| Locally advanced (inoperable) / metastatic treatment | 30 (19.4) | 23 (17.2) | 53 (18.3) |
| 0 | 12 (7.7) | 20 (14.9) | 32 (11.1) |
| 1 | 107 (69.0) | 79 (59.0) | 186 (64.4) |
| 2 | 31 (20.0) | 29 (21.6) | 60 (20.8) |
| 3 | 5 (3.2) | 6 (4.5) | 11 (3.8) |
Adapted from the TRUQAP Product Monograph1
ECOG PS=Eastern Cooperative Oncology Group performance status; WHO=World Health Organization.
* TRUQAP is only indicated for patients with PIK3CA/AKT1/PTEN alterations.
TRUQAP + fulvestrant demonstrated statistically significant improvement in PFS vs. placebo + fulvestrant*
In patients with PIK3CA/AKT1/PTEN-altered tumours (n=289) (40.8% of the overall population) ![]()
Adapted from the TRUQAP Product Monograph1
Demonstrated:
50% reduction in risk of progression or death with TRUQAP + fulvestrant vs. fulvestrant HR=0.50† (95% CI: 0.38, 0.65; p<0.001‡)
Number of events (%): TRUQAP + fulvestrant 121 (78.1) vs. fulvestrant 115 (85.8)
CI=confidence interval; HR=hazard ratio; mPFS=median progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumours.
* Analysis was performed by investigator assessment determined by RECIST 1.1.
† Stratified Cox proportional hazards model. A hazard ratio <1 favours capivasertib + fulvestrant.
‡ Stratified log-rank test.
Improvement in PFS observed across pre-specified subgroups
Subgroups included:
- presence of visceral metastases,
- prior exposure to CDK4/6 inhibitors and
- in the non-altered tumour population which comprised patients with a confirmed non-altered tumour and those with no testing result available.1*
71% of the overall trial patients received prior CDK4/6i1
* TRUQAP is only indicated for patients with PIK3CA/AKT1/PTEN alterations.
Overall survival analysis in patients with PIK3CA/AKT1/ PTEN-altered tumours (secondary endpoint)
A preliminary assessment of OS (30% maturity) at the time of the primary PFS analysis did not suggest a detrimental effect on survival of treatment with TRUQAP plus fulvestrant compared with placebo plus fulvestrant.1 The 30% maturity rate was calculated based on the 87 events in the 289 patients from the PIK3CA/AKT1/PTEN-altered population.6,7
Adapted from Turner, et al.4
Tick marks indicate censored data. A 0.01% alpha penalty was assigned to the overall survival analyses of no detriment (i.e., with the HR not favouring the fulvestrant-only group); a sufficient number of deaths for a formal analysis of overall survival had not occurred by the data-cutoff date.