- Roche's targeted cancer therapy entrectinib drove strong response rates in patients whose tumors harbor a rare genetic mutation, trial results presented Sunday showed, helping to validate the Swiss pharma's decision from last year to buy the drug's developer, Ignyta.
- Yet the data may not be enough to put entrectinib ahead of Loxo Oncology and partner Bayer's rival larotrectinib, which is currently under review for approval by the Food and Drug Administration. Fresh figures also unveiled Sunday proved larotrectinib's high efficacy held up in a larger group of patients than previously shown.
- Both therapies aim to treat cancer based not on tumor site, but rather the presence of a genetic rearrangement known as TRK fusion, which can spur malignant growth across different cells and tissue in the body.
Loxo's therapy, which Bayer bought into last year, is already under the microscope at the FDA, with a decision on approval expected by late November.
Investors, then, looked to the annual meeting of the European Society for Medical Oncology for insight into the challenge Roche's entrectinib could present.
"These data will be key to determining the competitive threat to larotrectinib," wrote Leerink analyst Andrew Berens in an Oct. 8 note ahead of the ESMO conference, which runs through Tuesday. Previous data on entrectinib mainly came from patients with another mutation.
Data compiled from three early studies showed entrectinib shrank tumors in 31 out of 54, or roughly 57%, of patients with TRK gene fusion cancers. Median duration of response stretched to just over 10 months.
Notably, the dataset included patients with 10 different solid tumor types, reflecting the pan-cancer potential of targeted therapies like entrectinib.
Entrectinib has also shown efficacy in treating non-small cell lung cancer with ROS1 mutations. Roche plans to submit the drug to global regulators for approval in that indication as well as TRK fusion cancer.
While good, the results reported by Roche will likely be compared to the profile Loxo's established for larotrectinib.
The company's submission to the FDA included data on 55 adult and pediatric patients with TRK gene fusion cancer. On Sunday, Loxo updated those numbers with an additional year of follow-up as well as data on 67 patients who were subsequently enrolled in the company's studies.
Across both data sets, 81% of 109 larotrectinib-treated patients responded — maintaining the high efficacy reported earlier by Loxo. Thirteen patients still awaiting initial response assessments were not included in the efficacy analysis.
Median duration of response was not reached, meaning more than half of responding patients remained in response at time of data cut-off.
Patients on Loxo's drug had 24 different tumor types, ranging from soft tissue sarcomas to breast, colon, lung cancer and melanoma.
Cross-trial comparisons can be challenging, given differences in patient characteristics, treatment regimens and, in the case of larotrectinib and entrectinib, cancer types.
Both therapies were generally well tolerated, most adverse events classified as Grades 1 and 2.
Through the deal with Bayer, the German drugmaker holds ex-U.S. rights to larotrectinib and a successor candidate known as LOXO-195. In the U.S., Loxo and Bayer will co-promote both products, if approved.
The success of larotrectinib and entrectinib is an example of the quickening pace of research aimed at rethinking how cancer is treated, targeting genetic make-up rather than a tumor's site of origin.
In May 2017, Merck & Co. won a landmark OK from the FDA for its immunotherapy Keytruda to treat any cancers that are microsatellite instability-high or mismatch repair deficient.
While promising, such an approach requires more comprehensive genetic testing to reveal which patients have targetable cancers.
Roche plans to lean on its subsidiary Foundation Medicine to use genomic profiling to identify patients who could benefit from entrectinib. Because mutations like TRK fusion are rare, so-called next-generation sequencing is needed to test tumors for dozens of genetic alterations at once.