A targeted drug from Novartis reduced the risk of breast cancer returning by 25% versus standard treatment when used after surgery in people vulnerable to a relapse, according to clinical trial data released Friday.
The findings, which will be presented at the American Society of Clinical Oncology’s annual meeting in Chicago, give Novartis a chance at Food and Drug Administration approval for its drug in this so-called adjuvant setting. A competing therapy from Eli Lilly won a similar OK a year and a half ago.
Novartis announced in March that the trial, called NATALEE, had succeeded, but didn’t disclose details. The full findings now released give breast cancer doctors an opportunity to evaluate how the drug, known as ribociclib and sold as Kisqali, might fit in treatment.
“While early, these results are very promising and suggest that there will be a role for adjuvant ribociclib,” Rita Nanda, MD, director of the breast oncology program at the University of Chicago and an expert ASCO asked to review the data, said in a statement.
Novartis’ and Lilly’s drugs are both part of a class of cancer medicines known as CDK 4/6 inhibitors, and have become central to their respective makers’ plans in oncology. Sales, while initially modest, have grown as the drugs proved helpful beyond their initially approved use in treating metastatic disease.
Novartis’ data will invite comparisons to Lilly’s drug, Verzenio, in this setting. Testing previously showed Verzenio reduced the risk of recurrence by 35% compared to hormone therapy. However, since the two medicines haven’t been tested head-to-head in a trial, neither drug can be declared superior.
Participants in Novartis’ trial were diagnosed early with a type of breast cancer that can be treated with hormone drugs but not with therapies like Herceptin that target a protein called HER2. This type of tumor, referred in shorthand as HR+ and HER2-, accounts for roughly 70% of all breast cancer cases in the U.S.
Participants’ tumors were also typically small and had spread no further than the skin or chest wall.
With current therapy, the odds of long-term survival are good, although between one-third to one-half of patients relapse, sometimes long after initial treatment, said Dennis Slamon, division chief of hematology/oncology at the University of California, Los Angeles, who is presenting the data at ASCO.
The study enrolled 5,101 men and pre- or postmenopausal women, who received either Kisqali or a placebo on top of hormone therapy. In a pre-planned analysis, researchers reported tumor recurrence in 189 participants who took Kisqali, or about 7%, compared with 237, or about 9%, of those who only got hormone treatment.
Among the people who were followed through three years, 90% on Kisqali were alive and free of cancer, compared with 87% of those on only hormone drugs.
Low white blood cell counts and joint pain were the most common adverse events reported in participants receiving Kisqali, and rates of gastrointestinal side effects were “low,” researchers reported.
NATALEE and the study Lilly used to support Verzenio’s post-surgery use differed in one key way. While Lilly’s trial enrolled only patients in whom tumors had spread to at least one lymph node, NATALEE included patients considered “node-negative.”
At a press conference held by ASCO, Slamon said Kisqali lowered recurrence risk by 37% in node-negative trial participants, who numbered about 600. The comparatively small size of the group means the significance of that finding is less certain, although Slamon characterized it as “highly suggestive” of a benefit.
Nanda, of University of Chicago, said Kisqali would be a welcome treatment addition for those patients, if approved. “Recurrences can be quite delayed, and for our patients with node negative disease, to this point, we haven’t seen any improvements with the addition of a CDK4/6 inhibitor,” she said at the press conference.
The results fell short of Jefferies analyst Peter Welford’s expectations. Heading into the trial, Welford had projected Kisqali would reduce the risk of disease progression by at least 30%, data that would support peak sales of $3.4 billion in the adjuvant setting. Welford, in a note published Friday morning, lowered that estimate to about $2.7 billion, saying the data Novartis revealed were “closer to our downside scenario.”
Vijayakrishna Gadi, deputy director of the University of Illinois Cancer Center, said the NATALEE findings “move the needle in a good way” because Kisqali may be easier for patients to take. “[Verzenio] is more challenging to tolerate,” he said. “That’s probably what’s going to win the day. It’s really going to come down to what is the easier drug to tolerate.”
Kisqali costs at least $6,000 a month, and if taken over the course of several years could lead to substantially higher costs for insurers and, through co-pays and co-insurance, patients. About half of patients taking Kisqali in clinical trials for metastatic breast cancer had stopped taking it after two years because their disease had progressed. In NATALEE, by comparison, study participants were still taking it through three years.
Kisqali had sales of $1.2 billion in 2022, a 31% increase from 2021. Verzenio sales, meanwhile, grew 84% to nearly $2.5 billion last year, boosted by the drug’s October 2021 approval in the adjuvant setting.
