Multimodal Care Is Key Focus at Breast Cancer Conference

Sara A. Hurvitz, MD

As long-awaited results from pivotal trials are revealed during major medical conferences, community oncologists in the clinic look forward to the resulting approvals with much anticipation. That focus continues to be the hallmark of the upcoming 20th Annual International Congress on the Future of Breast Cancer® West, hosted by Physicians’ Education Resource®, LLC (PER®).¹

Cochair Sara A. Hurvitz, MD, said the intensive, 2-day conference provides a multimodal perspective on care that includes medical oncology, radiation oncology, and surgical oncology.

“It’s a fantastic way for physicians to [learn about] the latest research results that can be translated for use in the clinic,” she said in an interview with Targeted Therapies in Oncology. Hurvitz is an associate professor in the Department of Medicine at the David Geffen School of Medicine, codirector of the Santa Monica-UCLA Outpatient Hematology/Oncology Practice, and medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit at UCLA in Los Angeles, California.

Hurvitz is moderating the morning session on July 30, which will cover breast cancer management with curative intent. One of the presentations during her session is being made by Joyce O’Shaughnessy, MD, cochair of Breast Cancer Research and chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center and The US Oncology Network in Dallas, Texas, and cochair of the conference. Hurvitz expects O’Shaughnessy’s presentation, “Neo/Adjuvant CDK4/6 Inhibitors: Ready for Prime Time?” to address updated results from the monarchE trial (NCT03155997) and the MONALEESA-7 trial (NCT02278120), both of which evaluated various CDK4/6 inhibitors combined with estrogen therapy.

In monarchE, investigators demonstrated that adding abemaciclib (Verzenio) to standard adjuvant endocrine therapy continued to improve invasive disease–free survival among patients with high-risk, node-positive, early-stage, hormone receptor–positive, HER2-negative breast cancer.²

In the phase 3 MONALEESA-7 trial, patients with hormone receptor–positive, HER2-negative breast cancer had a significant improvement in overall survival (OS) and chemotherapy delay when treated with ribociclib (Kisqali) plus endocrine therapy compared with placebo.³

At a median follow-up of 53.5 months (range, 46.9- 66.4), the median OS with ribociclib plus endocrine treatment was 58.7 months vs 48.0 months with placebo/endocrine therapy (HR, 0.763; 95% CI, 0.608-0.956), translating to a 24% relative reduction in the risk of death with the CDK4/6 inhibitor.

Moreover, data from a subgroup analysis examining survival in relation to endocrine partner, results showed that patients who received a nonsteroidal aromatase inhibitor (NSAI) experienced a median OS of 58.7 months with ribociclib/endocrine therapy versus 47.7 months with placebo/endocrine therapy (HR, 0.798; 95% CI, 0.615-1.04).

Immune Checkpoint Inhibitors

Turning to immunotherapy in breast cancer, Hurvitz acknowledged that it is an exciting strategy for certain tumor types but that in breast cancer, results have been somewhat limited.

“Immunotherapy in breast cancer has been shown to be somewhat beneficial, but those benefits are limited to tumors that are PD-L1 positive in the frontline setting, rather than in later lines,” Hurvitz said.

For example, updated efficacy results from the IMpassion130 trial (NCT02425891) evaluated 902 patients; 451 were randomly assigned to receive atezolizumab (Tecentriq) plus nab-paclitaxel, and 451 were assigned to receive placebo plus nab-paclitaxel (the intention-to-treat population).⁴

Median overall survival in the intention-to-treat patients was 21.0 months (95% CI, 19.0-22.6) with atezolizumab and 18.7 months (95% CI, 16.9- 20.3) with placebo (stratified HR, 0.86; 95% CI, 0.72-1.02; P = .078). In the exploratory OS analysis in patients with PD-L1 immune cell– positive tumors, median OS was 25.0 months (95% CI, 19.6-30.7) with atezolizumab versus 18.0 months (95% CI, 13.6-20.1) with placebo (stratified HR, 0.71, 95% CI, 0.54-0.94).

Somewhat limited benefits have also been reported for other immune checkpoint inhibitors. Improved progression-free survival (PFS) was observed with pembrolizumab (Keytruda) and chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer in the KEYNOTE-355 trial (NCT02819518).⁵

At the second interim analysis for KEYNOTE-355, median follow-up was 25.9 months for patients in the pembrolizumab-chemotherapy group and 26.3 months in the placebo-chemotherapy group. Among patients with a combined positive score (CPS) of 10 or more, median PFS was 9.7 months with pembrolizumab-chemotherapy and 5.6 months with placebo-chemotherapy (HR, 0.65; 95% CI, 0.49-0.86; P = .0012). Median PFS was 7.6 and 5.6 months (HR, 0.74; 95% CI, 0.61-0.90; P = .0014), respectively, among patients with a CPS of 1 or more and 7.5 and 5.6 months (HR, 0.82; 95% CI, 0.69- 0.97) among the intention-to-treat population.

“The benefits of pembrolizumab were restricted to those patients with a CPS of 10 or greater, which is not the majority of patients with triple-negative breast cancer,” Hurvitz said.

A Matter of Resistance

Turning to CDK4/6 inhibitors, Hurvitz noted that despite the benefits observed in PFS and OS for this particular class of drugs, resistance continues to be a challenge, prompting investigators to evaluate next-generation CDK4/6 inhibitors.

“The success of CDK4/6 inhibitors in drug development has been outstanding,” she said. “My hope for the future is that we’re going to have better agents for triple-negative breast cancer and [that] we’ll see an improvement in survival with this disease subtype in the future,” Hurvitz said.

_References:

_{1. 20th Annual International Congress on the Future of Breast Cancer® West. Physicians’ Education Resource®, LLC (PER®). Accessed March 16, 2021. https://bit.ly/2OwiDPA}

_{2. O’Shaughnessy J, Johnston S, Harbeck, N, et al. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020; virtual. Abstract GS1-01.}

_{3. Tripathy D, Im S-A, Colleoni M, et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy (ET) +/- ribociclib. Presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020; virtual. Abstract PD2-04. https://bit. ly/3cGIzQq}

_{4. Schmid P, Rugo HS, Adams S, et al; IMpassion130 Investigators Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;21(1):44-59. doi:10.1016/S1470- 2045(19)30689-8}

_{5. Cortes J, Cescon DW, Rugo HS, et al; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable 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}