In a phase 3 trial of Zejula in certain types of breast cancer, GSK’s bid to track tumor cells at the molecular level has helped patients catch metastatic disease before symptoms set in.
While that’s good news for people who were able to start treatment of metastatic cancer earlier, the result ultimately spelled the end for GSK’s study.
In April, GSK “permanently” discontinued enrollment in ZEST, a late-stage study from 2021 aiming to recruit 800 patients with either HER2-negative, BRCA-mutated breast cancer or triple-negative breast cancer with molecular disease. The move doesn’t portend any problems with Zejula itself, instead reflecting “eligibility challenges” that made enrollment “much more challenging than previously thought,” GSK said in its first-quarter earnings update.
Specifically, fewer than 5% of the 800 patients have been randomized so far, a GSK spokesperson explained over email.
GSK’s study leveraged new circulating tumor DNA (ctDNA) testing technology to pinpoint patients at higher risk of disease recurrence for potential treatment with Zejula while their disease burden was still low. CtDNA refers to DNA fragments released into the bloodstream by dying tumors.
To qualify for Zejula treatment in ZEST, breast cancer patients needed to have finished “definitive upfront treatment,” aka surgery and other neoadjuvant and adjuvant treatment. They also needed to have a positive ctDNA test and, critically, could not have radiologically detectable disease.
As it turns out, however, “the prevalence of radiologically detectable metastatic disease among patients who are ctDNA positive is much higher than expected,” GSK’s spokesperson added in a company statement.
Patients who received a positive ctDNA test were given other screens, including a CT scan, before their eligibility for the Zejula trial could be confirmed.
“This enabled the identification of asymptomatic metastatic disease sooner than would typically have been detected, since routine CT scans are not the standard of care in this population,” GSK explained.
GSK stressed the issue was related to enrollment hurdles, not Zejula itself, and clarified that the ZEST cancellation “does not impact any other ongoing trials with niraparib,” referring to the medicine’s generic name.
GSK will carry on with studies of Zejula in a range of other tumors types, including lung, ovarian and childhood cancers. The company remains committed to precision medicine technology like ctDNA testing, too, which GSK says enables patients to “have access to more customized treatment decisions.”
Breast cancer patients already have the option of rival PARP inhibitors to tackle their disease, with Pfizer’s Talzenna and Merck and AstraZeneca’s Lynparza already approved for the indication.
Zejula, for its part, boasts green lights in ovarian cancer, fallopian tube cancer and peritoneal cancer. GSK’s PARP drug brought home 114 million pounds sterling worldwide in 2023’s first quarter, the British drugmaker said Wednesday.
Back in November, GSK followed an FDA request to restrict Zejula’s second-line maintenance ovarian cancer indication in the U.S. to only cover patients with germline BRCA mutation. Previously, GSK had pulled Zejula’s approval in late-line ovarian cancer.
But, according to the company’s earnings report, first-line growth of Zejula in the U.S. “more than offset” any reduction in the second-line setting.