Physician Views: Is the HER2-positive breast cancer extended adjuvant opportunity big enough to support neratinib's blockbuster forecasts?

Physician Views: Is the HER2-positive breast cancer extended adjuvant opportunity big enough to support neratinib's blockbuster forecasts?

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Published on Jul 28, 2014

Top-line data from the ExteNET study - which were released earlier this week - appear to establish Puma Biotechnology's neratinib as a viable therapy for use in the extended adjuvant setting for HER2-positive breast cancer. Data indicates that treatment with neratinib for 12 months following standard 12-month therapy with Herceptin increases disease-free survival by 33 percent versus placebo.

Significantly, there appear to be no other products in development for usage in this setting. With Roche's Herceptin generating annual sales of around $4 billion in the adjuvant setting, analysts have been quick to ascribe blockbuster potential to neratinib - see ViewPoints: Puma's perfect storm - share price triples on new breast cancer data.

The data come as something of a surprise. Partly as the ExteNET study is a legacy of Pfizer's development of neratinib (Puma in-licensed the compound in 2011 and have primarily focused on its development in neo-adjuvant HER2-positive breast cancer) and partly as previous efforts to extend duration of therapy in adjuvant patients have delivered less than compelling data.

Most notably, the HERA study failed to demonstrate any benefit from extending adjuvant therapy with Herceptin from one to two years. Nevertheless, this has not prevented some commentators from arguing that a more valid study design would be to compare a combination of neratinib and Herceptin to Herceptin monotherapy during a second year of adjuvant therapy (rather than compare neratinib to placebo as the ExteNET study does). Puma has partially defended the study design by suggesting that neratinib has demonstrated effectiveness in patient subsets where Roche's newer HER2 therapies Perjeta and Kadcyla have not. This could differentiate the product and thus ensure longer-term use in the extended adjuvant setting even if Roche is successful in shifting the standard of care for adjuvant patients via its two newer therapies.

Puma is also yet to unveil any safety data from ExteNET, but has cautioned that the rate of grade 3 diarrhoea could be as high as 30 percent. In subsequently initiated studies of neratinib, Puma has employed Imodium prophylaxis to combat this side effect and hopes to reduce the rate to between 5 percent and 10 percent in a real-world setting.

To initially ascertain the commercial opportunity for neratinib based on top-line data from ExteNET, FirstWord is this week polling US and EU5-based oncologists. Specifically we are asking them...
  • What percentage of adjuvant HER2-positive breast cancer patients (who have received standard 12-month therapy with trastuzumab) they estimate are eligible for further treatment?
  • How they would describe the significance of newly announced data for neratinib within the context of disease management for adjuvant HER2-positive breast cancer patients?
  • How feasible and acceptable is the suggestion that use of Imodium is expected to reduce diarrhoea rates to between 5 percent and 10 percent in a real-world setting?
  • To what percentage of adjuvant HER2-positive breast cancer patients (who have received standard 12-month therapy with trastuzumab) they would you expect to prescribe neratinib to 12 months after it becomes available?
  • To what percentage of the same patient group (in the same setting) they would expect to prescribe neratinib to three years after launch?