Table 2.
Targeting PI3K/Akt pathway post CDK4/6 inhibitor: results of phase III SOLAR-1(alpelisib arm), phase II BYLieve and phase III CAPItello-291 (capivasertib arm) trial studies.
| BYLieve Cohort A | BYLieve Cohort B | BYLieve Cohort C | SOLAR-1 Alpelisib arm, PIK3CA-mutated cohort | CAPItello-291 Capivasertib arm, ITT population | |
|---|---|---|---|---|---|
| N | 127 | 126 | 126 | 169 | 355 |
| Cohort details | Immediate prior AI + CDK4/6i | Immediate prior fulvestrant + CDK4/6i | Immediate prior CT or ET | Recurrence/progression on/after AI | Prior ET, prior CDK4/6i allowed |
| Treatment arm | Fulvestrant + alpelisib | Letrozole + alpelisib | Fulvestrant + alpelisib | Fulvestrant + alpelisib | Fulvestrant + capivasertib |
| Median prior lines of palliative treatment | 1 | 1 | 2 | 1 | 1 |
| Prior CDK4/6i in metastatic setting (%) | 100 | 100 | 66.7 | 5.3 | 69.0 |
| Prior CT in metastatic setting (%) | 6.3 | Not available | 46.0 | 0 | 18.3 |
| Prior fulvestrant (%) | 0 | 100 | 32.5 | 0 | 0 |
| Median PFS (months) (95% CI) | 7.3 (5.6–8.3) | 5.7 (4.5–7.2) | 5.6 (5.4–8.1) | 11.0 (7.5–14.5) | 7.2 (5.5–7.4) |
| Median OS (months) (95% CI) | 17.3 (17.2–20.7) | Not reported | Not reported | 39.3 (34.1–44.9) | Not mature |
| ORR (%) (95% CI) | 17 (11–25) | 15.7 | 24.3 (16.8–33.2) | 26.6 (20.1–34.0) | 22.9 |
| Discontinuation due to AE (%) | 20 | 14.3 | 15.1 | 25.4 | 13 |
| AEs, % (all/≥ grade 3) | 99/67 | 100/69.8 | 99.2/67.5 | 99.3/76.0 | 96.6/41.7 |
| Hyperglycemia | 69/29 | 63.5/25.4 | 65.1/23.8 | 63.7/36.6 | 16.3/2.3 |
| Rash | 29/10 | 31.0/9.5 | 38.9/13.5 | 35.6/9.9 | 38.0/12.1 (all types) |
| Diarrhea | 60/6 | 67.5/4.0 | 52.4/3.2 | 57.7/6.7 | 72.4/9.3 |
| Nausea | 46/0 | 54.8/2.4 | 40.5/2.4 | 44.7/2.5 | 34.6/0.8 |
| Fatigue | 29/1 | 31.0/4.0 | 31.1/4.0 | 24.3/3.5 | 20.8/0.6 |
| Reference | Rugo et al.65 | Rugo et al.66 | Rugo et al.67 |
André et al.58 André et al.64 |
Turner et al.74 |
AI aromatase inhibitor, CDK4/6i cyclin-dependent kinase 4/6 inhibitor, CT chemotherapy, ET endocrine therapy, ORR objective response rate, OS overall survival, PFS progression-free survival.