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"This is not a treatment for a patient with limited bone involvement with a very low volume of disease…or for somebody 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."

Eric Winer, MD, director, Yale Cancer Center; president, physician-in-chief, Smilow Cancer Hospital, discusses crucial considerations for the use of inavolisib (Itovebi) plus palbociclib (Ibrance) with fulvestrant (Faslodex) in the advanced setting for select patients with hormone receptor (HR)–positive, HER2-negative breast cancer, following 

the FDA approval of this regimen in October 2024.

During an FDA special session moderated by Winer at the 

2024 San Antonio Breast Cancer Symposium (SABCS)

, discussion centered on the FDA approval process, including key factors considered when defining the appropriate patient population for new agents.

For inavolisib, the consensus was that this regimen should be reserved for patients who develop metastatic disease while on endocrine therapy or within 1 year of completing adjuvant endocrine therapy, Winer reports. Importantly, the combination is not intended for those presenting with de novo stage IV disease, he notes. The study population primarily consisted of patients with visceral metastases, indicating that this approach is best suited for individuals with a more aggressive disease course where additional intervention beyond hormonal therapy is warranted, he says.

Conversely, patients with limited bone involvement or low-volume disease, even in visceral sites, may not be ideal candidates for this regimen, Winer continues. The rationale is to maximize treatment benefit in those at higher risk of rapid disease progression, ensuring prolonged disease control with the most effective first-line approach, he explains. These considerations underscore the need for careful patient selection when integrating novel targeted agents into clinical practice, Winer concludes.

Videos

Eric Winer, MD, discusses considerations for inavolisib plus palbociclib with fulvestrant in PIK3CA-mutated, HR-positive, HER2-negative breast cancer.

Dr Winer on Considerations for Inavolisib Plus Palbociclib and Fulvestrant in PIK3CA-Mutated HR+/HER2– Breast Cancer

Dr Winer on the Rationale for the TakeAim Leukemia Trial in Mutated AML

Eric Winer, MD, clinical director, Adult Leukemia, institute physician, Dana-Farber Cancer Institute; assistant professor, medicine, Harvard Medical School, discusses 

the phase 1/2a TakeAim Leukemia trial (NCT04278768)

 investigating emavusertib (previously CA-4948) in patients with relapsed or refractory 

- and spliceosome-mutated acute myeloid leukemia (AML), as well as key efficacy findings from this study.

Notably, data from the investigation were presented at the 

. The TakeAim Leukemia trial was designed to determine the effectiveness of IRAK4 inhibition in promoting cell death in AML cells and high-risk myelodysplastic syndrome cells, Eric begins. This trial focused on 2 patient populations: those with 

 mutations and those with spliceosome mutations, he states. Treatment with emavusertib in patients with mutated AML reportedly demonstrated anti-leukemic activity and exhibited a manageable safety profile. The encouraging aspect of the TakeAim Leukemia trial is that its results aligned with expectations based on preclinical data, demonstrating that the drug performed as anticipated, Winer reports.

In practical terms, more than 50% of patients experienced a reduction in blast counts, with significant responses observed in the 

-mutated and spliceosome-mutated groups, Winer expands. This finding confirmed the study’s hypothesis and demonstrated a clear antileukemic effect with the agent, paving the way for further trials, he states. Additionally, in the 

-mutated disease group, the IRAK4 inhibitor was effective against both 

 ITD and TKD mutations. Among the 12 patients treated within the 

-mutated subgroup, 6 patients experienced responses, and 4 patients achieved complete remission (CR) or CR with incomplete blood count recovery, Winer emphasizes.

These results illustrate a targeted effect of the IRAK4 inhibitor, highlighting its potential benefit for patients with specific genetic mutations, he says. The trial’s success in proving the mechanism of action and efficacy of emavusertib offers promising implications for future therapeutic strategies and trials, Winer concludes.

Eric Winer, MD, discusses the rationale for the phase 1/2a TakeAim Leukemia trial of emavusertib in patients with R/R FLT3- and spliceosome-mutated AML.

Eric Stephen Winer, MD, assistant professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the FDA approval of ivosidenib (Tibsovo) in acute myeloid leukemia (AML).

May 2, 2019, the FDA approved a supplemental new drug application (sNDA) for ivosidenib as monotherapy for the frontline treatment of adult patients with 

-mutant AML, as detected by an FDA-approved test, who are ≥75 years old or are ineligible to receive intensive chemotherapy. Data from a phase I trial served as the basis for the approval. In the trial, ivosidenib induced a 28.6% (95% CI, 13.2-48.7) complete response (CR) rate and a CR plus CR with partial hematologic recovery (CRh) rate of 42.9% (95% CI, 24.5-62.8). The median durations of CR and CR+CRh were not estimable, and 41.7% (n = 5) of patients who achieved CR/CRh remain on ivosidenib as of the data cutoff.

This approval brings yet another targeted treatment option with significant benefit to patients with 

Eric Stephen Winer, MD, assistant professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the FDA approval of ivosidenib in acute myeloid leukemia (AML).

Eric Stephen Winer, MD

Articles

Dr Winer on Considerations for Inavolisib Plus Palbociclib and Fulvestrant in PIK3CA-Mutated HR+/HER2– Breast Cancer

Dr Winer on the Rationale for the TakeAim Leukemia Trial in Mutated AML

Dr. Winer Discusses the FDA Approval of Ivosidenib in AML