- Highly anticipated clinical results from Roche showed the Swiss pharma's immunotherapy Tecentriq benefited patients with a difficult-to-treat type of breast cancer, but the relatively modest improvement observed in the study could limit the drug's use to a smaller subgroup.
- In the IMpassion 130 trial, first-line treatment with Tecentriq plus Abraxane extended progression-free survival among patients with metastatic triple-negative breast cancer (TNBC) by about two months over chemotherapy alone. Interim data on overall survival showed a numerical advantage for the Tecentriq group, but those results were not statistically significant.
- Patients who expressed high levels of a biomarker known as PD-L1, however, did better than those who tested negative. Roche on Saturday said it is seeking regulatory approval for the Tecentriq combination only in TNBC patients who are PD-L1 positive, a subgroup estimated to represent about 40% of the overall population.
Expectations for Tecentriq (atezolizumab) had run high since announcement of its topline success in IMpassion 130 in July. While rival Merck & Co. has largely sewn up a leading position in non-small cell lung cancer, TNBC represents an open opportunity for cancer immunotherapy.
Metastatic TNBC, which describes tumors that lack estrogen and progesterone receptor expression and don't overexpress HER2, is associated with particularly poor outcomes. Median overall survival (OS) is typically less than 18 months.
Tecentriq's positive Phase 3 results in TNBC mark a first among cancer immunotherapies, according to Roche, and put it ahead of the competition — for now.
Yet the detailed results presented Saturday at the annual meeting of the European Society for Medical Oncology could leave investors disappointed.
Median progression-free survival for patients given Tecentriq and Abraxane (albumin-bound paclitaxel) reached 7.2 months, versus only 5.5 months for those on chemo alone — a relative risk reduction of 20%. Survival results showed a nearly four-month edge to Tecentriq treatment, but that data did not clear statistical significance at the interim analysis.
Tecentriq was also associated with more serious adverse events than chemo, and more patients on the immunotherapy had immune-related adverse events.
In PD-L1 positive patients, though, a stronger PFS benefit was observed, as well as a nearly 10 month improvement in survival among Tecentriq-treated patients. As statistical significance was not met among all patients, the OS benefit among PD-L1 expressing patients wasn't formally tested.
"While the benefit in terms of progression-free survival was relatively small, around three months, the gain in overall survival in the PD-L1 positive subgroup was impressive with a ten-month benefit," said Marleen Kok, a medical oncologist at the Netherlands Cancer Institute in Amsterdam, in a statement issued by ESMO.
Investors who listened to Roche's earnings call this week might have expected such results after Roche's head of pharmaceuticals, Daniel O'Day, indicated that PD-L1 positive patients drove most of the benefit.
Roche will seek approval in TNBC, but a restriction on use to just PD-L1 expressors could limit the commercial opportunity for the pharma.
A recent company presentation suggested Roche expects a revenue opportunity of between 500 million Swiss francs to 1 billion Swiss francs (about $500 million to $1 billion) — figures that had appeared conservative to some analysts.
Credit Suisse analyst Vamil Divan estimates that Roche currently has as much as an 18-month lead over its immunotherapy rivals in TNBC. That advantage could soon dissipate, though, as Merck and others drive clinical programs forward.
Merck's Keytruda (pembrolizumab), for instance, is currently being tested in several Phase 3 TNBC studies that are expected to read out data in November and December of this year. Given the similar mechanism of action between the drugs, a broad-based benefit for Keytruda might now be seen as less certain.
Yet, while Roche is first, its results leave room for improvement.