The competition between Clovis Oncology and AstraZeneca that has been simmering for years in the T790M-positive non-small-cell lung cancer (NSCLC) arena will soon boil over into a full-blown battle for scripts if the companies manage to stick to their respective timelines. Clovis’ rociletinib is slightly ahead in the race to market after it completed a rolling NDA this month, which could lead to an approval early next year, while AstraZeneca’s AZD-9291 looks to be just a few months behind, with a projected launch slated for mid-2016.
There is no doubt about the unmet need these agents will be serving, as the T790M mutation is thought responsible for causing approximately half of all cases of acquired resistance to treatment with earlier iterations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI), including Roche’s Tarceva (erlotinib), AstraZeneca’s Iressa (gefitinib) and Boehringer Ingelheim’s Gilotrif (afatinib).
What is less clear, however, is how physicians will decide between the competing third-generation EGFR-TKIs, and how aggressive they will be about prescribing rociletinib and/or AZD-9291 as front-line therapy rather than using them in second-line after resistance develops. (See Analyst Notes: The race is on between AstraZeneca and Clovis to capitalise on the EGFR-TKI resistant NSCLC population.)
Abstracts published online ahead of this month’s World Conference on Lung Cancer recently offered the latest look at how the two agents are stacking up against one another. While mature progression-free survival data are not yet available, the activity profiles appear relatively in-line with one another as AZD-9291 achieved response rates of 58 percent and 64 percent in a pair of Phase II trials, whereas two dose levels of rociletinib generated response rates of 54 percent and 60 percent.
Some differentiation on safety has emerged between the products, with the key side effects being hyperglycaemia for rociletinib and rash for AZD-9291. Specifically, 17 percent and 24 percent of patients receiving the lower and higher doses of rociletinib were diagnosed with grade 3/4 hyperglycaemia, while 37 percent and 40 percent of those receiving AZD-9291 in the two studies developed a rash.
To gain better understanding about the views of doctors on how they think the agents stack up against one another, and where they are likely to fit into the armamentarium for NSCLC, FirstWord PLUS is polling US- and EU5-based oncologists and asking them…
1. How do you feel rociletinib or AZD-9291 differentiated itself from the other at this point?
2. How likely are you to prescribe rociletinib and AZD-9291 sequentially?
3. In separate Phase II trials, rociletinib achieved a 37-percent response rate in T790M-negative patients, while AZD-9291 achieved a 21-percent response rate in this setting. How convinced are you that this will translate into a clinically meaningful difference in T790M-negative patients in Phase III testing?
4. How do you primarily expect to use rociletinib and AZD-9291 in T790M-positive patients (based on currently available data/your level of enthusiasm for these products)?
5. Rociletinib and AZD-9291 are each being tested in front-line treatment in patients with mutant EGFR who have not been screened for T790M status. What progression-free survival benefit (versus Tarceva/Iressa) do you feel one of the third-generation agents need to achieve in order to drive moderate penetration in this front-line setting?
You will be able to read the results and analysis later this week.
Results and related analysis will be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.
As always, FirstWord would very much like to receive your feedback and suggestions.
