MD Anderson at SABCS

ABSTRACTS: RF01-04 and RF01-07

Two studies led by researchers at The University of Texas MD Anderson Cancer Center demonstrated clinical benefit from novel targeted therapies, which may offer new treatment options for patients with metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The data will be shared in oral presentations today at the 2023 San Antonio Breast Cancer Symposium (SABCS).

According to the National Cancer Institute, HR+/HER2− breast cancer is the predominant breast cancer subtype in the U.S., constituting nearly 70% of all breast cancer cases. When caught at an early stage before it metastasizes, the disease is very treatable. However, the five-year relative survival rate for metastatic HR+/ HER2- breast cancer is only 34%, underscoring the need for innovative therapeutic approaches.

Futibatinib achieves antitumor activity in advanced breast cancer with FGFR1 amplification (Abstract RF01-04)
The Phase II FOENIX-MBC2 trial, led by Senthil Damodaran, M.D., Ph.D., associate professor of Breast Medical Oncology and Investigational Cancer Therapeutics, achieved early signs of antitumor activity when combining the FGFR inhibitor futibatinib with the hormone therapy fulvestrant in patients with advanced HR+/HER2− breast cancer harboring high-level FGFR1 amplification.

Among 22 patients, the researchers observed a median progression-free survival (PFS) of 7.2 months. The overall response rate (ORR) was 18.2%, including four confirmed partial responses, and the median duration of response was 6.3 months.

“We are encouraged by the antitumor activity of futibatinib and the possibility of offering this targeted therapy to patients who have had their breast cancer progress after CDK4/6 inhibitor treatment,” Damodaran said. “We will continue to observe these patients and study further biomarkers of response.”

This open-label multicenter trial enrolled patients with locally advanced/metastatic breast cancer harboring FGFR gene amplifications who had progressed on prior CDK4/6 inhibitor treatment. Patients were enrolled in one of four treatment cohorts based on diagnosis and FGFR gene amplification status. Patients were a median age of 58 years, had received a median of three lines of any prior systemic anticancer therapy, and had all received previous CDK4/6 inhibitor treatment.

No treatment-related serious adverse events were reported. The most common treatment-related adverse events were hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%) and dry mouth (40.9%).

The trial was supported by Taiho Oncology, Inc. Damodaran previously served on the Taiho advisory board. A complete list of collaborating authors and their disclosures can be found in the abstract.

Tinengotinib shows clinical benefit in heavily pre-treated patients with metastatic HR+/HER2- or triple-negative breast cancers (Abstract RF01-07)
Pooled data from two trials led by Sarina Piha-Paul, M.D., associate professor of Investigational Cancer Therapeutics, demonstrated clinical benefit with manageable side effects from tinengotinib, either alone or in combination with nab-paclitaxel, in heavily pre-treated patients with metastatic HR+/HER2- or triple-negative breast cancers.

In 11 patients with HR+/HER2- breast cancer, tinengotinib monotherapy achieved an ORR of 45.5%, a clinical benefit rate (CBR) of 64% and a median progression-free survival (mPFS) of 5.68 months. The 17 patients with triple-negative breast cancer had an ORR of 23.5%, a CBR of 29.4% and a mPFS of 2.73 months. Of note, partial responses were seen in three patients designated as HER2-zero and in two patients designated HER2-low.

"Tinengotinib has showcased clinical benefit for individuals facing refractory metastatic HR+/HER2- or triple-negative breast cancers, potentially elevating treatment outcomes," Piha-Paul said. "This positive impact was also observed among subgroups, including patients with HER2-zero and HER2-low disease."

[PA1] The presentation pooled data from a Phase I study and a Phase Ib/II study. Among the 36 patients treated across both trials, 30 patients were treated with tinengotinib alone and six were treated with tinengotinib plus nab-paclitaxel. Twenty-eight patients receiving tinengotinib monotherapy were evaluated for efficacy. Patients were a median age of 51 years old and had received a median of five lines of prior therapy. All patients had no available standard treatment options.

No treatment-related serious adverse events were reported. The most common treatment-related adverse events of tinengotinib monotherapy were hypertension (60.0%), stomatitis (50.0%), palmar-plantar erythrodysesthesia syndrome (46.7%) and diarrhea (20.0%). The most common treatment-related adverse events of tinengotinib in combination with nab-paclitaxel were neutrophil count decreased/neutropenia (50.0%), stomatitis (50.0%), hypertension (33.3%), hyponatremia (33.3%), hypokalemia (33.3%), and nausea (33.3%). One patient on the combination had a grade-five pulmonary hemorrhage.

The trial was supported by TransThera Sciences (Nanjing), Inc. Piha-Paul reports research support from TransThera Bio. A complete list of collaborating authors and their disclosures can be found in the abstract.

ABSTRACT: GA03-03

Targeted treatment with ribociclib plus hormone therapy provided significant invasive disease-free survival (iDFS) benefits in patients with early-stage hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer at risk of disease recurrence. Results from the Phase III NATALEE trial, led by researchers at The University of Texas MD Anderson Cancer Center, were presented today at the 2023 San Antonio Breast Cancer Symposium (SABCS).

Patients who received the combination therapy experienced significantly extended iDFS — the period before the first occurrence of invasive disease — compared to those who underwent hormone therapy alone, which corresponds to a 25% reduction in the risk of recurrence. The iDFS rates at three years were 90.7% with the combination and 87.6% with only hormone therapy.

"The current treatments we have for HR+/HER2- early-stage breast cancer only help a small group of patients, which leaves many people with limited options to lower the chances of their cancer coming back,” said Gabriel Hortobagyi, M.D., professor of Breast Medical Oncology. “This study shows the continued disease-free survival improvement for patients receiving ribociclib with hormone therapy and showed a benefit across clinically relevant subgroups.”According to the National Cancer Institute, HR+/HER2- breast cancer is the most common subtype, accounting for nearly 70% of all breast cancer cases in the United States. Approximately one-third of individuals diagnosed with stage II HR+/HER2- breast cancer face a risk of recurrence, despite receiving standard-of-care treatment. Among those with stage III disease, more than half experience a recurrence.

Ribociclib belongs to a category of targeted therapies known as small-molecule inhibitors. It specifically targets the CDK4 and CDK6 proteins, which play a crucial role in regulating cell growth and promoting the growth of breast cancer cells. The Food and Drug Administration has granted approval for ribociclib's use in treating advanced HR+/HER2- breast cancer. While previous research led by Hortobagyi demonstrated the survival advantages of ribociclib in treating metastatic breast cancer, this trial provided evidence that it could improve outcomes for patients with early-stage breast cancer that hasn’t spread to the lymph nodes.

The NATALEE trial enrolled 5,101 men and pre-/post-menopausal women from 20 different countries with stage IIA, IIB, or III HR+/HER2- breast cancer at risk for recurrence. Participants were randomized to receive either adjuvant ribociclib for three years with hormonal therapy for at least five years or hormonal therapy alone for at least five years. The primary endpoint was iDFS, and the secondary efficacy endpoints were recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS).

Researchers observed consistent benefits across patient subgroups, including those with node-negative, stage II and stage III disease. Analyses of secondary endpoints of DDFS and RFS supported ribociclib with hormone therapy compared to ribociclib alone. The overall survival data remains incomplete as of now, with 84 patients in the ribociclib plus hormone therapy group and a total of 88 events in the hormone therapy alone group.

No new safety signals were observed since the prior interim analysis, and side effects were consistent with the known safety profile of ribociclib and non-steroidal aromatase inhibitors.

“I am encouraged by the results of this treatment combination in early-stage breast cancer patients,” Hortobagyi said. “We will continue to follow the patients long-term, but these results could impact how we treat this disease in the future.”

Researchers will continue to evaluate how adding ribociclib to hormonal therapy impacts quality of life and will follow patients to observe long-term outcomes.

The study was sponsored by Novartis Pharmaceuticals, which markets ribociclib (Kisqali). Hortobagyi is a paid consultant for Novartis, and MD Anderson received funds from Novartis to conduct this study. A complete list of collaborating authors and disclosures can be found in the abstract.