u200c Inavolisib plus palbociclib and fulvestrant may become new standard in PIK3CA-mutated, HR+ and HER2- breast cancer

Inavolisib plus palbociclib and fulvestrant (fulvestrant) may be a new standard of care for patients with PIK3CA-mutated, hormone receptor (HR) -positive, HER2-negative advanced breast cancer, according to researchers. In the phase 3 INAVO120 trial, adding inavolisib to palbociclib and fulvestrant more than doubled median progression-free survival (PFS). inavolisib also has a tendency to improve overall survival (OS).

The INAVO120 trial (Identifier: NCT04191499) includes 325 patients with PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer. Patients experienced recurrence during or within 12 months of completing adjuvant endocrine therapy, and they had not received prior treatment for advanced breast cancer. Patients were randomly assigned to receive inavolisib plus palbociclib and fulvestrant (n=161) or placebo plus palbociclib and fulvestrant (n=164) until disease progression or unacceptable toxicity. Baseline characteristics were generally similar between the two groups. Inavolisib was administered at 9 mg daily during each 28-day cycle. On days 1-21, administer 125 mg of palbociclib daily. Fulvestrant 500 mg was administered on days 1 and 15 of cycle 1, but on day 1 of each subsequent cycle.

At a median follow-up of 21.3 months, 42% of patients in the inavolisib group and 30% of patients in the control group remained on treatment. Median PFS was 15.0 months in the inavolisib group and 7.3 months in the control group (hazard ratio [HR] 0.43; 95% CI 0.32-0.59; P<0.0001). The 6-month disease-free survival rates were 82.9% and 55.9% respectively. The 12-month PFS rates were 55.9% and 32.6%, respectively. The 18-month PFS rates were 46.2% and 21.1%, respectively. Median OS was not reached in the inavolisib group, compared with 31.1 months in the control group (HR, 0.64; 95% CI, 0.43-0.97; P=0.0338). The predetermined limits for OS were not crossed (P value of 0.0098 or HR of 0.592), so this is not a significant difference.

The 6-month overall survival rate was 97.3% in the inavolisib group and 89.9% in the control group. The 12-month overall survival rates were 85.9% and 74.9% respectively. The 18-month overall survival rates were 73.7% and 67.5% respectively. The overall response rates in the inavolisib group and control group were 58.4% and 25.0%, respectively. The median duration of response was 18.4 months and 9.6 months (HR, 0.57; 95% CI, 0.33-0.99). The clinical benefit rates were 75.2% and 47.0% respectively. Inavolisib plus palbociclib and fulvestrant had a manageable safety profile consistent with that of the individual drugs.

Common grade 3-4 adverse events (occurring in the inavolisib group and the control group respectively) were neutropenia (80.2% vs. 78.4%), thrombocytopenia (14.2% vs. 4.3%), leukopenia (6.8% vs. 10.5%) and anemia (6.2% vs. 1.9%). Grade 3-4 events that occurred in the inavolisib group but not the control group included hyperglycemia (5.6% vs 0%), diarrhea (3.7% vs 0%), stomatitis and mucosal inflammation (5.6% vs 0%), and nausea (0.6% vs 0%). There were 6 fatal adverse events in the inavolisib group and 2 in the control group, but these events were not related to treatment.

PalbociclibThe original drug has been launched in China and has been included in medical insurance. Currently, reimbursement is only available to patients who meet the indications. The common specifications100mg*21 pills may cost more than 6,000 yuan per box, while the original drug sold overseas is more expensive. The price of 125mg*21 pills per box may be around 10,000 yuan (the price may fluctuate due to exchange rates). Palbociclib generics are also sold overseas. The ingredients of the drug are basically the same as those sold domestically and abroad, but the price is cheap. For example, the price of a box of 125mg*21 tablets produced by a Bangladesh pharmaceutical factory may be several hundred yuan (the price may fluctuate due to the exchange rate).