Conference Pivots Toward SERDs, Early TNBC

Publication
Article
Targeted Therapies in OncologyJanuary 2022
Volume 11
Issue 1
Pages: 55

Debu Tripathy, MD, said the 39th Annual Miami Breast Cancer Conference is always a well-rounded meeting.

Debu Tripathy, MD

Debu Tripathy, MD

Taking a personalized and adaptive approach to managing breast cancer, which emphasizes the importance of assessing patient response and escalating or de-escalating drug therapy as appropriate, will be explored during the 39th Annual Miami Breast Cancer Conference® sponsored by Physicians’ Education Resource®, LLC (PER®), March 3-6, 2022.

Attendees will learn about managing specific toxicities, including unique algorithms and treatment options for managing cardiotoxicities. The conference’s cochair, Debu Tripathy, MD, will provide a primer on genomics that highlights very rare mutations and novel treatment options that are being explored.

"We want [every] clinician who treats breast cancer to understand the entire picture, even if it’s outside of their area of specialty,” Tripathy, professor and chair of the Department of Breast Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, said during an interview with Targeted Therapies in Oncology™. “We want surgeons to know about genomics, and we want medical oncologists to know about postoperative pain management.”

Selective Estrogen Receptor Degraders/Downregulators

Tripathy noted that the “Emerging Data on Oral Selective Estrogen Receptor Degraders and Other Novel Hormonal Therapies” presentation during the morning plenary session on March 4 is not to be missed. He expects data from the recent San Antonio Breast Cancer Symposium (SABCS) to be shared with attendees.

The fundamental treatment for estrogen receptor–positive subtypes remains endocrine therapy with novel compounds such as CDK4/6 inhibitors or PI3K inhibitors, which have improved progression-free survival and overall survival in these patients.

However, some patients still develop endocrine resistance after or during endocrine treatment.

Selective estrogen receptor degraders/downregulators (SERDs) are a class of agents currently in research and development against aromatase inhibitor resistance or tamoxifen resistance. During SABCS, results from a dosing and activity trial (NCT03363893) evaluating samuraciclib (CT7001), a once-daily, oral, small molecule selective inhibitor of CDK7, were presented.1

The study enrolled 31 patients who received either 240 mg of samuraciclib by mouth once daily plus 500 mg of fulvestrant every 4 weeks (n = 6) or 360 mg of samuraciclib by mouth once daily plus 500 mg of fulvestrant every 4 weeks (n = 25). Investigators observed a clinical benefit rate (CBR) in 36% of patients at 24 weeks. Patients without liver metastases had a CBR of 55%. The CBR rose from 36% to 53% when excluding patients with a TP53 mutation. Samuraciclib has been granted fast track status by the FDA.2

Triple-Negative Breast Cancer

From a historical perspective, standard chemotherapy has been the mainstay of treatment for patients with early-stage triple-negative breast cancer (TNBC). However, resistance to chemotherapy remains a clinical challenge and there remains a need to identify novel therapies to improve outcomes and discern which patients would benefit.

“We are going to be exploring how to manage these patients with early-stage TNBC because the treatment landscape is evolving,” Tripathy said. “We are now using immunotherapy for these patients.”

In November 2020, the FDA granted accelerated approval to pembrolizumab (Keytruda) in combination with chemotherapy as treatment for patients with locally recurrent unresectable or metastatic TNBC whose tumors have demonstrated PD-L1 expression with a combined positive score of 10 or greater.2 The approval was based on results of the phase 3 KEYNOTE-355 trial (NCT02819518), which examined chemotherapy plus either the PD-1 inhibitor or matched placebo.3

Investigators reported that adding pembrolizumab to chemotherapy significantly improved progression-free survival (PFS) vs chemotherapy alone among patients with previously untreated locally advanced inoperable or metastatic TNBC who had a combined positive score of at least 10. Specifically, the median PFS was 9.7 months with pembrolizumab/chemotherapy vs 5.6 months with placebo/chemotherapy (HR, 0.65; 95% CI, 0.490.86; P =.0012).

In the phase 3 KEYNOTE-522 (NCT03036488) trial, pembrolizumab was added to chemotherapy for high-risk (stage II/III) TNBC in the neoadjuvant setting. Results showed that at a median follow-up of 39.0 months, 84.5% of patients who received pembrolizumab plus chemotherapy were alive and had not experienced an event vs 76.8% of those who received chemotherapy alone (HR, 0.63; 95% CI, 0.48-0.82; P =.00031).4

Another trial in the neoadjuvant setting evaluated adding pembrolizumab to chemotherapy (I-SPY2; NCT01042379).5 This was a phase 2 randomized trial for patients with high-risk stage II/III disease. In the multiarm trial, investigators reported that adding pembrolizumab to neoadjuvant chemotherapy more than doubled the pathologic complete response rate in hormone receptor–positive/HER2-negative and triple-negative patients with cancer.

A Hybrid Meeting

Ongoing concerns about health and safety throughout the COVID-19 pandemic has resulted in the 39th Annual Miami Breast Cancer Conference®, chaired by Patrick I. Borgen, MD, to follow a hybrid format, with in-person and virtual components. “Taking advantage of a hybrid conference allows us to have a larger faculty that includes international experts,” Tripathy said.

Tripathy said the 39th Annual Miami Breast Cancer Conference® is always a well-rounded meeting. “I think it’s important that the meeting is multidisciplinary. We have pathologists, radiologists, medical oncologists, and surgical oncologists all together,” he said. “We believe that it takes a village [to deliver care], and when a patient has breast cancer, they often have to see 1 or more specialists. We consider this a team effort.”

REFERENCES:

1. Coombes C. Study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in combination with fulvestrant in patients with advanced hormone receptor positive HER2 negative breast cancer (HR+BC). Presented at: 2021 San Antonio Breast Cancer Symposium; December 9, 2021; San Antonio, TX.

2. Carrick Therapeutics receives FDA fast track designations for two samuraciclib combinations for the treatment of HR+, HER2- advanced breast cancer and locally advanced or metastatic triple negative breast cancer. News release. Accessed December 15, 2021. https://bit.ly/3J4NtX1

3. FDA grants accelerated approval to pembrolizumab for locally recurrent unresectable or metastatic triple negative breast cancer. FDA. November 13, 2020. Accessed November 19, 2020. https:// bit.ly/32VvoqP

4. Cortes J, Cescon DW, Rugo HS, et al; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inopera-ble or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828. doi:10.1016/S0140-6736(20)32531-9

5. Schmid P, Cortes J, Dent R, et al. KEYNOTE-522: phase III study of neoadjuvant pembrolizumab + chemotherapy vs placebo + chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC. Ann Oncol. 2021;32(9):1198-1200. doi:10.1016/j. annonc.2021.06.014

6. Nanda R, Liu MC, Yau C, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the on-going phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):676-684. doi:10.1001/jamaoncol.2019.6650

Related Videos
Erika P. Hamilton, MD, and the Oncology Brothers presenting slides
Erika P. Hamilton, MD, and the Oncology Brothers presenting slides
Erika P. Hamilton, MD, and the Oncology Brothers presenting slides
Erika P. Hamilton, MD, and the Oncology Brothers presenting slides
Erika P. Hamilton, MD, and the Oncology Brothers presenting slides
Related Content