One of Eli Lilly’s most important pipeline prospects is breast cancer candidate abemaciclib, but new phase III data suggest the company could have its work cut out differentiating the drug from its rivals.
The MONARCH 3 trial was reported at the European Society of Medical Oncology (ESMO) conference in Madrid over the weekend, and showed that the CDK4/6 inhibitor prolonged progression-free survival (PFS) by 46% when added to hormonal therapy as a first-line treatment for postmenopausal women with HR+/HER2 negative breast cancer.
That seems to be comparable to the benefit seen with two already-marketed drugs in the class – Pfizer’s Ibrance (palbociclib) and Novartis’ Kisqali (ribociclib). While there is no head-to-had data available for the three drugs, the finding is arguably a little disappointing as Lilly had pitched abemaciclib as being significantly more potent than its rivals, and amenable to continuous dosing rather than intermittent dosing, which has raised hopes of a more potent effect.
Lilly will hope that its drug will be preferred because of its side-effect profile, and in particular is hoping that what appears to be a reduced tendency to cause neutropenia could prove to be a big factor for prescribers and patients. It is associated with diarrhoea however, although Lilly says this can be managed with anti-diarrhoeal drugs such as loperamide.
If its safety profile is not a differentiating factor, Lilly will be forced to compete toe-to-toe with Ibrance, which is well-established in the marketplace, as well as new entrant Novartis which was approved earlier this year. Ibrance saw sales almost triple to reach $2.1bn last year and has been tipped by EvaluatePharma to become a $6bn-plus product in 2022, with Kisqali and abemaciclib vying for second place in the market.
The trial also threw out some data that could have a bearing on all CDK4/6 inhibitors, namely that around one-third of women may not need a CDK 4/6 inhibitor as initial treatment because some patients – including those with bone metastases or indolent disease – may do well with endocrine therapy alone.
“It is well known that these patients have a better prognosis than those with liver or lung metastases, or who relapse early during the course of adjuvant endocrine therapy,” said lead investigator Angelo Di Leo of Istituto Toscano Tumori in Prato, Italy.
“In our study, nearly one-third of patients had bone metastases only or a tumour relapsing several years after stopping adjuvant endocrine therapy,” continued Di Leo. “This is a clinically relevant proportion of patients for whom we may consider delaying use of a CDK 4/6 inhibitor.”
That view was echoed by Giuseppe Curigliano of the European Institute of Oncology (IEO) in Milan, Italy, who said that with three positive trials of CDK4/6 inhibitors ” he major question that still needs to be answered is the optimal sequence of treatment”.
“Should we use these agents in the first line setting or is there a space to start with endocrine therapy alone and to add CDK 4/6 inhibitors at progression?” he asked, suggesting an academic-driven trial should be conducted to answer that question.