Attendees during the San Antonio Breast Cancer Symposium (SABCS) being held at the Henry B. Gonzalez Convention Center in San Antonio, TX. Photo courtesy © 2019 AACR/SABCS / Todd Buchanan.
Attendees during the San Antonio Breast Cancer Symposium (SABCS) being held at the Henry B. Gonzalez Convention Center in San Antonio, TX. Photo courtesy © 2019 AACR/SABCS / Todd Buchanan.

Neoadjuvant (pre-surgery) treatment with the CDK4/6 inhibitor ribociclib (Kisqali®; Novartis) in combination with the aromatase inhibitor letrozole (Femara®; Novartis) produced response rates similar to multi-agent chemotherapy in patients with high-risk luminal B breast cancer.

This is the conclusion based on results from the SOLTI-1402/CORALLEEN trial, funded by Novartis, the Breast Cancer Research Foundation, the American Association for Cancer Research (AACR), and Breast Cancer Now Career Catalyst.

The data, presented at the San Antonio Breast Cancer Symposium (SABCS), held December 10-14, 2019 in San Antonio, Texas, were published simultaneously in The Lancet Oncology.[1][2]

Luminal B breast cancer
Luminal B breast cancer is characterized by a lower expression of estrogen receptor (ER), a low expression of progesterone receptor (PR negative), HER2 positive and a high histologic grade. These cancers are defined by aggressive clinical behavior and have a relatively poor prognosis. According to the 2013 St Gallen Consensus, the luminal B breast cancer accounts for nearly 40% of all breast cancers.[3][4]

J Gavilá speaks during the San Antonio Breast cancer Symposium (SABCS) held at the Henry B. Gonzalez Convention Center in San Antonio, TX. Photo courtesy © 2019 AACR/SABCS Todd Buchanan.
Joaquin Gavilá, MD, medical oncologist at the Instituto Valenciano de Oncologia (IVO) in Valencia, Spain, who is also a member of the governing board at the SOLTI Breast Cancer Research Group,  speaks during the San Antonio Breast cancer Symposium (SABCS) held at the Henry B. Gonzalez Convention Center in San Antonio, TX. Photo courtesy © 2019 AACR/SABCS Todd Buchanan.

Current standard of care
“The current standard treatment for high-risk luminal B breast cancer is neoadjuvant chemotherapy, but this is associated with high levels of toxicity,” noted Joaquin Gavilá, MD, medical oncologist at the Instituto Valenciano de Oncologia (IVO) in Valencia, Spain, who is also a member of the governing board at the SOLTI Breast Cancer Research Group.

“Neoadjuvant endocrine therapy is an alternative to chemotherapy, but it has not shown high levels of efficacy for high-risk breast cancer,” Gavilá, explained

“Finding an effective alternative to multi-agent chemotherapy for patients with high-risk breast cancer is a priority,” he added.

Earlier studies
Previous studies showed that combining endocrine therapy with CDK4/6 inhibitors, drugs designed to prevent cancer cells from dividing, resulted in similar response rates to chemotherapy for metastatic breast cancers.

“We already knew that the combination of endocrine therapy with CDK4/6 inhibitors was efficacious in advanced breast cancers, so we were interested in investigating the efficacy of this combination for high-risk, early-stage breast cancer,” Gavilá explained

Study design
In this study, a parallel-arm, multicentre, randomized, open-label, phase II trial completed across 21 hospitals in Spain, the authors examined the efficacy of the CDK4/6 inhibitor ribociclib in combination with the aromatase inhibitor letrozole in patients with high-risk, luminal B, stage I to IIIA operable breast cancer.

The study enrolled 106 patients, who were randomly assigned 1:1 to receive either the ribociclib and letrozole combination or multi-agent chemotherapy as neoadjuvant treatment. The intention-to-treat analysis included 101 patients who had tissue samples available at the time of surgery.

At the time of surgery, 48% of the 49 patients in the ribociclib plus letrozole treatment arm had low risk of recurrence scores, as measured by PAM50, compared to 47.1% of the 52 patients treated with chemotherapy. Intrinsic subtype conversion to luminal A, which is a less aggressive subtype, occurred in 88% of patients in the ribociclib plus letrozole arm and in 84.3% of the chemotherapy arm.

Rates of low residual cancer burden were 8% in the ribociclib plus letrozole arm and 11.8% in the chemotherapy arm. Rates of PEPI 0, another indicator of favorable prognosis, were 24% in the ribocliclib-letrozole arm and 17.6% in the chemotherapy arm.[4][5]

Grade 3 and 4 toxicities were observed in 54.9% of patients in the ribociclib plus letrozole arm compared to 69.2% of patients in the chemotherapy arm.

“Our results indicate that neoadjuvant treatment with a combination of ribociclib and letrozole has similar clinical benefits as standard multi-agent chemotherapy, and with less toxicity,” said Gavilá.

“We believe that this combination is worth exploring as an alternative to chemotherapy for patients with high-risk luminal B breast cancer.”

However, Gavilá cautioned that the results are preliminary and need to be confirmed in future clinical trials.

Clinical trial
Neoadjuvant Multi-agent Chemotherapy or Letrozole Plus Ribociclib in Luminal B/HER2-negative Breast Cancer. (CORALLEEN) – NCT03248427

References
[1] Primary results of SOLTI-1402/CORALLEEN phase 2 trial of neoadjuvant ribociclib plus letrozole versus chemotherapy in PAM50 Luminal B early breast cancer: An open-label, multicenter, two-arm, randomized study. GS2-06. Presented during the 2019 San Antonio Breast Cancer Symposium (SABCS). [Abstract]
[2] Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): an open-label, multicentre, randomised, phase 2 trial [published online ahead of print, 2019 Dec 11]. Lancet Oncol. 2019;S1470-2045(19)30786-7. doi:10.1016/S1470-2045(19)30786-7 [Article]
[3] Harbeck N, Thomssen C, Gnant M. St. Gallen 2013: brief preliminary summary of the consensus discussion. Breast Care (Basel). 2013;8(2):102–109. doi:10.1159/000351193
[4] Li ZH, Hu PH, Tu JH, Yu NS. Luminal B breast cancer: patterns of recurrence and clinical outcome. Oncotarget. 2016;7(40):65024–65033. doi:10.18632/oncotarget.11344
[5] Ellis MJ, Tao Y, Luo J, et al. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008;100(19):1380–1388. doi:10.1093/jnci/djn309