RIGHT Choice: Ribociclib Plus ET Improves PFS vs Chemo
In the phase 2 RIGHT Choice trial, ribociclib combined with ET prolonged progression-free survival (PFS) when compared with combination chemotherapy in patients with aggressive, HR-positive, HER2-negative advanced breast cancer.2
The trial (ClinicalTrials.gov Identifier: NCT03839823) enrolled pre- or peri-menopausal patients who had received no prior systemic therapy for advanced disease. Patients were required to have aggressive disease, which was defined as having symptomatic visceral metastases, rapid disease progression, impending visceral compromise, or markedly symptomatic nonvisceral disease.
A total of 222 patients were randomly assigned to receive:
- Ribociclib (600 mg daily; 3 weeks on, 1 week off) plus goserelin and either letrozole or anastrozole (n=112)
- Investigators’ choice of chemotherapy, which was docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine (n=110).
Baseline characteristics were well balanced between the treatment arms. Per investigator judgment, 54.5% of patients in the ribociclib-ET arm and 50% in the combination chemotherapy arm had visceral crisis.
At a median follow-up of 24.1 months, 45.5% of patients in the ribociclib-ET arm and 23.6% of patients in the chemotherapy arm remained on treatment. The median time on study treatment was 15 months with ribociclib plus ET and 8.6 months with chemotherapy.
Patients in the ribociclib-ET arm had a near doubling of PFS compared with patients who received combination chemotherapy. The median PFS was 24.0 months and 12.3 months, respectively (hazard ratio, 0.54; 95% CI, 0.36-0.79; P =.0007). The PFS benefit was consistent across most patient subgroups.
The median time to treatment failure was more than twice as long for ribociclib-ET as for chemotherapy — 18.6 months and 8.5 months, respectively (hazard ratio, 0.45; 95% CI, 0.32-0.63).
The overall response rate was 65.2% in the ribociclib-ET arm and 60.0% in the chemotherapy arm. The median time to response was 4.9 months with ribociclib plus ET and 3.2 months with chemotherapy (hazard ratio, 0.78; 95% CI, 0.56-1.09).
OS results were immature at the data cutoff.
There were no new safety signals for patients receiving ribociclib plus ET. Treatment-related serious adverse events (AEs) occurred in 1.8% of patients in the ribociclib-ET arm and 8.0% of patients in the chemotherapy arm. Treatment discontinuation due to AEs occurred in 7.1% and 23.0%, respectively.
“These findings suggest that, through the use of first-line ribociclib plus endocrine therapy, we may be able to avoid or delay chemotherapy and spare patients — even those with aggressive, life-threatening disease — the toxicities and discontinuations associated with chemotherapy,” study presenter Yen-Shen Lu, MD, PhD, of National Taiwan University Hospital in Taipei, said in a statement.8
CAPItello-291: Adding Capivasertib to Fulvestrant Doubles PFS
In the phase 3 CAPItello-291 trial, adding the AKT inhibitor capivasertib to fulvestrant doubled the PFS in patients with HR-positive, HER2-negative advanced breast cancer.3
The trial (ClinicalTrials.gov Identifier: NCT04305496) included 708 patients who had previously received aromatase inhibitor therapy, with or without a CDK4/6 inhibitor. The patients were randomly assigned to receive either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off), each in combination with fulvestrant (500 mg on days 1 and 15 in cycle 1, then every 4 weeks).
The researchers evaluated outcomes in the overall population and among patients with AKT pathway alterations. The AKT pathway-altered population had to have at least 1 qualifying alteration in PIK3CA, AKT1, or PTEN.
In the overall population, there were 355 patients in the capivasertib arm and 353 in the placebo arm. In the AKT pathway-altered population, there were 155 patients in the capivasertib arm and 134 in the placebo arm.
Baseline characteristics were generally well balanced between the treatment arms in the overall population and the AKT pathway-altered population. In the overall population, most patients were women (99.2% in the capivasertib arm and 98.9% in the control arm), were postmenopausal (80.8% and 73.7%, respectively), and had received 1 prior line of treatment for advanced breast cancer (80.6% and 71.4%, respectively).
In the overall population, the median PFS was 7.2 months in the capivasertib arm and 3.6 months in the control arm (hazard ratio, 0.60; 95% CI, 0.51–0.71; P <.001). In patients with AKT pathway alterations, the median PFS was 7.3 months and 3.1 months, respectively (hazard ratio, 0.50; 95% CI, 0.38–0.65; P <.001). OS results were immature.
Among all patients with measurable disease at baseline, the objective response rate was 22.9% in the capivasertib arm and 12.2% in the placebo arm. In the AKT pathway-altered cohort, capivasertib nearly tripled the objective response rate (28.8% with capivasertib vs 9.7% with placebo).
The most frequently reported grade 3 or higher AEs (in the capivasertib and placebo arms, respectively) were diarrhea (9.3% vs 0.3%), maculopapular rash (6.2% vs 0%), other rash (5.4% vs 0.3%), hyperglycemia (2.3% vs 0.3%), and stomatitis (2.0% vs 0%). AEs leading to discontinuation occurred in 13.0% of patients in the capivasertib arm and 2.3% of those in the placebo arm.
“The improvement in progression-free survival with relatively well-tolerated side effects is extremely encouraging,” study presenter Nicholas C. Turner, MD, PhD, of the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust in London, UK, said in a statement.9
“We are hopeful that capivasertib will become a new treatment option for patients whose cancer has progressed on a regimen containing an endocrine therapy,” he added.