After Trodelvy failed to impress in staving off tumor progression in HR-positive, HER2-negative breast cancer, Gilead placed a bet on the drug showing a life extension benefit. Now, the drugmaker has surprisingly returned with that win, but industry watchers remain skeptical.
Trodelvy beat chemotherapy at keeping patients with heavily pretreated HR-positive, HER2-negative breast cancer alive, Gilead said Monday. The improvement was statistically significant and clinically meaningful, the company added.
Trodelvy hit that positive readout at the second interim analysis of overall survival in the phase 3 TROPiCS-02 trial. Gilead said it has filed an FDA application in HR-positive, HER2-negative disease, which accounts for about 70% of new breast cancer diagnoses, a much larger population than in Trodelvy’s current triple-negative breast cancer use. But analysts remain unsure of the potential market size.
The initial readout from TROPiCS-02 was a disappointment for Gilead investors. In patients who had tried a median three lines of prior treatment, Trodelvy cut the risk of disease progression or death by 34%, which met the trial’s statistical significance bar. But industry watchers struggled with the magnitude of benefit, arguing that the mere 1.5-month improvement on delaying progression or death wasn’t clinically meaningful.
Once again, analysts have raised the same question of clinical meaningfulness for the patient survival results.
During the first analysis, Trodelvy cut the risk of death by 16%, which wasn’t statistically significant. At that time, 293 people in the trial had died, and Trodelvy extended patients’ lives by 1.6 months at the median, which, again, wasn’t considered clinically meaningful.
The trial’s second interim analysis was set to occur after 350 deaths. In a Monday note, Mizuho analyst Salim Syed questioned whether Trodelvy’s advantage would be that different now given only about an additional 20% deaths have occurred.
In a separate note, SVB Securities analysts said they will examine detailed data at an upcoming medical meeting to assess the data’s clinical meaningfulness and perhaps more importantly, the TROP2-targeted antibody drug conjugate’s position against AstraZeneca and Daiichi Sankyo’s rival HER2 ADC Enhertu.
Thanks to a landmark FDA approval, Enhertu just became the first HER2-targeted therapy for patients with previously treated HER2-low breast cancer. That indication covers HER2-low patients with HR-positive disease, which has a big overlap with the traditional HR+/HER2- group as used for recruitment in Trodelvy’s TROPiCS-02 trial. A physician survey by RBC Capital Markets previously showed that an average 39% of HR+/HER2- patients fit Enhertu’s HER2-low definition.
HR+/HER2- breast cancer has been billed as the next big market for Trodelvy—and Gilead’s overall oncology ambitions—after triple-negative disease. Based on the new overall survival win from TROPiCS-02, RBC analysts have on Monday increased their probability-weighted peak annual sales estimate for Trodelvy to $3.3 billion from the previous $2.7 billion.