“Impactful” Data Presentations Raise Hope in the Breast Cancer Field

In a conversation with CancerNetwork^® at the 2024 European Society for Medical Oncology (ESMO) Congress, Paolo Tarantino, MD, spoke about the most potentially impactful data to come from presentations in the breast cancer field.

Tarantino, an advanced research fellow at Dana-Farber Cancer Institute and Harvard Medical School, highlighted findings from 3 presentations that stood out to him at the meeting. These results came from the phase 3 KEYNOTE-522 study (NCT03036488) assessing perioperative pembrolizumab (Keytruda) plus chemotherapy in high-risk early-stage triple-negative breast cancer;¹ the phase 3b/4 DESTINY-Breast12 trial (NCT04739761) evaluating trastuzumab deruxtecan (T-DXd; Enhertu) for those with HER2-positive metastatic breast cancer with or without brain metastases;² and the phase 3 NATALEE trial (NCT03701334) investigating ribociclib plus nonsteroidal aromatase inhibitor therapy for those with hormone receptor (HR)–positive, HER2-negative early breast cancer.³

At the time of this conversation, Tarantino said that data from the NATALEE trial may lead to the FDA approval of ribociclib. Following the presentation of these findings at ESMO, the FDA approved ribociclib plus an aromatase inhibitor for patients with HR-positive, HER2-negative stage II and III early breast cancer.⁴

Transcript:

There were 3 very impactful abstracts at ESMO. There were many of them, of course, but [there were] 3 key ones.

One was the overall survival update from KEYNOTE-522. This was a trial that tested neoadjuvant and adjuvant pembrolizumab added to chemotherapy for triple-negative breast cancer. We knew that the addition of immunotherapy—of pembrolizumab—improved invasive disease-free survival [iDFS] in this population, and we’ve been using this treatment for patients with stage II and III triple-negative breast cancer. Finally seeing an improvement in overall survival with a Δ of [approximately] 6% and a benefit that is prolonged and maintained in time is striking because it confirms that we are saving the lives of patients with triple-negative breast cancer with immunotherapy.

Apart from that, we also saw the data from the DESTINY-Breast12 trial. DESTINY-Breast12 was a phase 3b/4 trial that tested trastuzumab deruxtecan in patients with HER2-positive breast cancer with or without brain metastasis. Most of the focus was on patients with brain metastases because this is the largest data set looking at T-DXd in this population. It showed a more than 70% intracranial response rate and 17 months of median progression-free survival [PFS]. T-DXd works amazingly well for patients with HER2-positive [disease with] brain metastasis. I do feel that these data position T-DXd even more strongly in the second line after the CLEOPATRA [NCT00567190] regimen for HER2-positive disease irrespective of brain [metastases].

Finally, with the NATALEE update, seeing that at 4 years, the addition of adjuvant ribociclib significantly improved [iDFS] for stage II and III HR–positive breast cancer was striking, especially because the Δ of 5% in iDFS [between arms] was very meaningful. There was a maintained hazard ratio improvement over time. I do feel that these data from NATALEE will lead to an approval of the drug. I feel there were improvements in all the subtypes of breast cancer, which raises hope in the field.

References

1. Schmid P, Cortés J, Dent RA, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: overall survival results from the phase I KEYNOTE-522 study. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. LBA4.
2. Lin N, Ciruelos EM, Jerusalem G, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. LBA18.
3. Fasching PA, Stroyakovskiy D, Yardley DA, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with HR+/HER2– early breast cancer: 4-year outcomes from the NATALEE trial. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. LBA13.
4. FDA approves Novartis Kisqali® to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed September 17, 2024. https://shorturl.at/p0jbc