ESMO: Lilly's Verzenio looks for an edge with gold-standard data in tough-to-treat patients

Eli Lilly's Verzenio is the only CDK 4/6 drug to offer data in certain tough-to-treat patient groups, executives say. (Eli Lilly/LinkedIn)

BARCELONA—It’s tough to be a third-to-market drug, particularly when you’re trailing a first-up launch like Pfizer’s blockbuster Ibrance. But with some new data showing Verzenio can help breast cancer patients live significantly longer, Eli Lilly’s hoping for a kick-start for its contender.

Follow-up data from the Monarch 2 trial in previously treated patients with HR-positive, HER2-negative breast cancer showed patients taking Verzenio on top of the hormone therapy fulvestrant lived a median 46.7 months versus 37.3 months for those treated with fulvestrant alone. That 9.4 survival advantage translates into a 25% cut to the risk of death.

The survival boost, reported Sunday at the European Society for Medical Oncology Congress, applied to women across the trial, be they pre-menopausal, peri-menopausal or post-menopausal. And the Verzenio patients also enjoyed a quality-of-life advantage; they went a median 50 months—more than four years—without needing follow-up chemotherapy, versus 22 months for women in the fulvestrant arm of the trial.

Those are stats Lilly’s happy to tout. But as Maura Dickler, Lilly VP of late-phase development, said in an interview ahead of the data release, the company’s also highlighting other numbers it believes set Verzenio apart from the crowd of CDK4/6 inhibitors—including Ibrance. Specifically, Verzenio’s results in women with particularly tough-to-treat disease.

“Verzenio is different,” Dickler said, pointing out that the trial enrolled patients who’d proven resistant to endocrine therapy, including those who’d relapsed quickly. The latter group also saw a “robust improvement in overall survival,” she said.

In fact, women with primary resistance to previous hormonal therapy saw “more pronounced effects” from Verzenio, the trial investigators pointed out, with a reduction in death risk of about 31%, shown by a hazard ratio of 0.686.

Likewise, Verzenio delivered particularly strong results for women whose tumors had spread through the abdomen, the study abstract noted, with a hazard ratio of 0.675, or a risk reduction of almost 33%.

“This is the only CDK4/6 data in those harder-to-treat populations,” Dickler said. The Monarch 2 numbers “are not only statistically significant, but really clinical meaningful.

“So often cancer trials show small survival benefits that don’t always translate into clinical practice. We feel that here, Verzenio really delivered a robust result.”

Lilly’s hoping it can parlay these data into broader use of Verzenio, but it faces a few hurdles in its path. For one, the company has to persuade doctors who now habitually use Ibrance, which launched back in February 2015, two and a half years before Verzenio’s October 2017 rollout.

It also faces at least one safety worry that so far doesn’t extend to Ibrance or to Verzenio’s other in-class rival, Kisqali from Novartis: Severe diarrhea. Lilly execs say it’s easily managed with anti-diarrheal medication, but Wolfe Research analyst Tim Anderson still figures it could hamper uptake. A second safety issue where Verzenio was singled out—at least at first—was severe lung disease; in May, Japan added a new safety warning to the med’s label, but earlier this month, the FDA put out its own warning, and it extended across the CDK4/6 class, not just to Verzenio.

Now that Monarch 2 has shown overall survival benefits, Lilly's waiting for another round of OS stats: The Monarch 3 trial in previously untreated women showed Verzenio could help patients live longer without their disease progressing, but hasn’t yet reached the median for overall survival.

The company’s also working on Monarch E, a test in women who’ve had their tumors removed—the so-called adjuvant setting—but specifically those with a worse prognosis, whether because of larger tumors, more lymph node involvement or high levels of Ki67, a biomarker of cellular proliferation. The data in tough-to-treat women in Monarch 2 “bodes well for good results” from that 4,500-patient adjuvant trial, expected in 2021, Dickler noted.

The Monarch 2 data were set for presentation in the same session as new data from Novartis’ rival drug Kisqali—the Monaleesa-3 study, which, like Monarch 2, paired the CDK4/6 product with fulvestrant. But Monaleesa focused only on the post-menopausal group, and included women who hadn’t been treated before and those on their second round of therapy. A separate Monaleesa trial looked at premenopausal women.