The Food and Drug Administration (FDA) has recently granted approval to Swiss company Roche’s inavolisib for treating HR-positive, HER2-negative breast cancer. The treatment has been approved for patients who are resistant to adjuvant endocrine therapy and have a PIK3CA mutation. The treatment is to be administered in combination with AstraZeneca’s Faslodex and Pfizer’s Ibrance.
PIK3CA mutations have been notoriously difficult to handle. Despite being known for decades, many drugs developed to target them have often had limited tolerability and efficacy.
Clinical data from the phase 3 INAVO120 trial enrolled patients with PIK3CA-mutated tumors that were considered endocrine-resistant. The results revealed that the risk of progression or death was significantly reduced by over 55% when Itovebi was added to Ibrance and Faslodex in the treatment schedules. In the control of the study, people went just over 7 months without disease progression, while in the Itovebi arm, the number was around 15 months.
A little over 6% of the patients experienced adverse events that led to the discontinuation of treatment, and the rate of adverse events was noted at around 24%.
High blood sugar levels, deemed grade 3 or 4 adverse events, have become common side effects for the PI3K class of drugs. Such adverse events were recorded at 5.6% in the Itovebi arm compared to 0% in the placebo group.
In the case of Novartis’ Piqray, hyperglycemia is also a known problem. The study through which Piqray earned its second-line approval, the phase 3 SOLAR-1 trial, revealed that 33.6% of patients on Novartis’ drug experienced grade 3 or 4 hyperglycemia, while only 0.6% of the control group suffered the same fate. In fact, the study identified hyperglycemia as the leading cause of adverse events in patients treated with Piqray.
It is understood that the degradation of regular PI3K causes hyperglycemia, and since Itovebi has improved specificity against the mutant PI3K alpha subunit, it is assumed to have a better efficacy and tolerability profile.
Apart from Piqray, AstraZeneca’s AKT inhibitor Truqap also finds its position in the market challenged by the presence of Itovebi. Before the approval of Roche’s drug, Piqray and Truqap were the big PI3K inhibitors in the market, with the latter having only recently been granted approval last year.
