- Pfizer's top-selling drug Ibrance has failed a second large Phase 3 trial in early-stage breast cancer, according to the drugmaker, which was testing the treatment in certain women whose tumors were at high risk of returning after surgery.
- Pfizer didn't disclose specific details from the study, called PENELOPE-B. But the company said Ibrance, when given alongside hormone therapy for five years, couldn't keep cancer in check any longer than hormone treatment alone in a study of roughly 1,250 women who had received chemotherapy before surgical removal of their tumors.
- The results solidify Eli Lilly's newfound advantage over Pfizer, after the company's rival medicine Verzenio succeeded in a similar study earlier this year. Ibrance has become a mainstay in the care of women whose breast cancer tumors have already spread, but earlier lines of care are viewed as the next opportunity for Ibrance and drugs like it.
Ibrance entered 2020 as the clear leader among a relatively new class of breast cancer medicines known as CDK 4/6 inhibitors. Sales of the drug in the year previous totaled $5 billion, far outpacing Verzenio and Novartis' similar treatment Kisqali.
The drug's success, however, was due to its use in the later stages of disease for women with the most common form of breast cancer, known as hormone receptor-positive. Pfizer had aimed to further set Ibrance apart by proving its worth earlier on, as an "adjuvant" treatment after surgery to remove a tumor.
Though considerable progress has been made in recent years to prevent cancer recurrence in patients with other forms of breast tumors, that hasn't been the case with HR-positive tumors, which grow slowly and don't usually respond well to chemotherapy.
Hormone therapy has been the standard of care for years and, despite its availability, nearly a third of women with HR-positive breast cancer will see their cancers return.
Pfizer, Lilly and Novartis have each run massive, lengthy trials to test the theory that adding their drugs to the mix could keep breast cancer at bay for longer. As it turns out, the standard treatment for hormone-positive patients may change, but not because of Ibrance.
Indeed, with news of the failure of PENELOPE-B, Ibrance has now fallen short in two large, multi-year adjuvant trials. The first, called PALLAS, tested Pfizer's drug and hormone therapy in a broad group of women and men with either Stage 2 or Stage 3 cancers and different risk levels for recurrence. Participants who received Ibrance fared worse than those on standard treatment.
PENELOPE-B, by contrast, enrolled patients more likely to see a recurrence, increasing the chances for Pfizer's drug to show a benefit. But expectations had dimmed after data presented at a medical meeting in September revealed Ibrance didn't much help a subset of high-risk patients in the PALLAS trial, either.
Pfizer's setbacks have left an opportunity for Lilly's Verzenio, which this year became the only CDK 4/6 inhibitor so far to be definitively shown to help keep HR-positive tumors from recurring. Those results came in patients with Stage 1 to Stage 3 cancer who were deemed at "high-risk" of recurrence based on certain disease markers. Lilly believes some 20,000 U.S. patients per year fit that description.
Breast cancer specialists interviewed by Biopharma Dive called the results practice-changing. But they also said adoption might be a challenge due to Verzenio's gastrointestinal side effects and the significant additional costs its use would add to adjuvant care. Lilly has said it intends to seek approval by the end of the year.
Verzenio could gain ground in the metastatic setting, too. In a note to clients, Evercore ISI analyst Umer Raffat speculated whether Ibrance's failures and Verzenio's recent victory might create a "halo effect" around Lilly's drug. Early evidence since Lilly's trial succeeded in June "doesn’t suggest that," he wrote, "but we'll track this dynamic over time."
Pfizer and Lilly will each report their latest quarterly sales figures on Oct. 27.
Doctor perceptions of the three drugs could shift once again when Novartis's adjuvant trial for Kisqali produces results. The study wraps up in 2022, though data could come earlier.