2024 FDA Approvals Highlight New Treatment Considerations in HR+ Breast Cancer

The FDA approvals of adjuvant ribociclib (Kisqali), along with inavolisib (Itovebi) plus palbociclib (Ibrance) with fulvestrant (Faslodex) in the advanced setting for select patients with hormone receptor (HR)–positive, HER2-negative breast cancer have initiated key treatment and regulatory considerations, including how the FDA reviews study data that leads to these types of approvals, according to Eric Winer, MD.

At the 2024 San Antonio Breast Cancer Symposium (SABCS), Winer moderated an FDA special session, which covered the September 2024 FDA approval of adjuvant ribociclib plus an aromatase inhibitor (AI) for the treatment of patients with HR-positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.1 He also highlighted the October 2024 approval of inavolisib plus palbociclib/fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.1,2

At the SABCS, a discussion delved into the approval of inavolisib plus palbociclib/fulvestrant and the utilization of progression-free survival (PFS) as a study end point.

“There was a very substantial improvement in PFS, but no improvement to date in overall survival [OS],” Winer, director of Yale Cancer Center, president and physician-in-chief at Smilow Cancer Hospital, New Haven, Connecticut, said in an interview with OncLive®. “Given the size of the trial, I'd be surprised if we ever see one, and [there was] no formal comparison of quality of life. Therefore, the question came up: is PFS a meaningful end point? The feeling was that it probably is, if [there’s] a really substantial improvement in PFS, and if the toxicity isn't excessive.”

In the interview, Winer discussed the significance of the FDA approvals of adjuvant ribociclib and inavolisib plus palbociclib/fulvestrant, and novel treatments emerging in the breast cancer landscape.

OncLive: What has been the significance of the FDA approval of adjuvant ribociclib for HR–positive, HER2-negative early breast cancer?

Winer: The session [at SABCS] really focused on 3 different topics, but 2 of them were recent FDA approvals. One was the FDA approval for adjuvant ribociclib in patients with HR–positive breast cancer supposedly at high risk [for recurrence]. The reason I say ‘supposedly’ is because some of the patients may not have been so high risk [in the phase 3 NATALEE trial (NCT03701334)].

In terms of ribociclib, we talked about the role that ribociclib plays in preventing recurrence, and we spent a fair amount of time talking about which patient population should be treated with ribociclib. The drug is approved for patients [at] high risk [of recurrence] with node-negative breast cancer. There was discussion about what the absolute benefits would be in such a patient and whether [the adjuvant use of ribociclib] makes sense. Of course, in the trial, only 10.5% of the patients had node-negative disease.

What are some crucial considerations following the FDA approval of inavolisib plus palbociclib and fulvestrant?

The other [recent FDA approval was] palbociclib with inavolisib, along with hormonal therapy [fulvestrant] for endocrine-resistant and PIK3CA-mutated metastatic breast cancer. In the session, we focused on what goes into their approval process. What factors does [the FDa] consider? How do they decide the patient population that they'll approve the agents? It’s important for people to understand how the FDA decides on a new drug having sufficient evidence [to support] an approval.

With the inavolisib study, where in fact, hormonal therapy was combined with both palbociclib and the PIK3CA kinase inhibitor, the big question is: who should get this? We all agreed that it should be patients who are either developing metastatic disease on endocrine therapy or within a year of receiving adjuvant endocrine therapy. This is not for patients who present up-front with de novo stage IV disease, and the vast majority of the patients in the study had visceral disease. This is not a treatment for a patient with limited bone involvement with a very low volume of disease, perhaps even in visceral sites, or for somebody, as I mentioned before, who has an up-front presentation.

It's [for] a population of patients where you're really worried about the impact that hormonal therapy will have. You want to take advantage of every bit of extra help you can [get] to ensure that the patient is going to do well for as long as possible on that treatment.

Are there any other novel breast cancer therapies in development that may impact the treatment paradigm?

There are so many breast therapies in development. There are antibody-drug conjugates and a whole range of new endocrine agents, mostly agents that target the ESR1 mutation. There will be new immunotherapy agents at some point in the future. The future in terms of breast cancer drug development is actually pretty good. Long past are the times when we would come to a meeting like [SABCS] and there'd be nothing new in a given year. Maybe we're a little greedy about it, but there's good reason to be greedy because we want to try to bring the best to patients as soon as possible. When we come to a meeting like [SABCS] or ASCO, we expect to hear about several new trials that will change practice. Therefore, what doctors, nurses, and, most importantly, patients can expect in the years ahead is a whole range of new treatment approaches.

References

1. FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2– early breast cancer. News Release Novartis. September 17, 2024. Accessed January 20, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-kisqali-reduce-risk-recurrence-people-hrher2-early-breast-cancer
2. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated HR–positive, HER2-negative, advanced breast cancer. FDA. October 10, 2024. Accessed January 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive