New treatment approaches and a growing portfolio of approved agents have significantly improved outcomes for breast cancer patients. However, many opportunities remain to improve the standard of care for these patients, according to Hope S. Rugo, MD, FASCO.
“I think back to less than 30 years ago when my mother had metastatic breast cancer, how few tools we had compared to what we have now,” Rugo said, adding that it was a catalyst for her to change careers from bone marrow transplant. bone to breast cancer research. “It has been an incredible journey to see what has happened in the last 23 years that I have been a breast cancer oncologist.”
At the Giants of Cancer Care® conference given during the 40th Annual CFS®, Rugo focused on the priorities for breast cancer research in 2022 and beyond, addressing key questions raised by his colleagues. Rugo, Professor of Medicine and Director of Breast Oncology Education and Clinical Trials at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, was the 2020 Giants of Cancer Care® Award Winner in the Education Category .
A theme at all times was communication. Ongoing discussions with colleagues, patients, nursing staff, and the community are key to speeding up and optimizing treatments.
Escalation, de-escalation and therapy optimization
The use of climbing Y de-escalation is not favored by the advocacy community, Rugo said, adding that these therapeutic adjustments should be referred to as “optimizing treatment for tumor biology and response to treatment. [In some ways] scaled Y de-escalation [imply] treatment intensity and even toxicity, and that is not the goal. [Rather,] the goal is not to have more [therapy]—is to have a smarter therapy.”
Speaking about approaches to developing smarter therapies, Rugo noted that understanding tumor biology and understanding biomarkers and genetic signatures are vital components of progress. “We have new study platforms that are helping us look [at] better ways to understand the efficacy of different combination treatments,” he said, adding that the search for new biomarkers is ongoing.
A focus on refining the use of checkpoint inhibitors in populations of women with breast cancer will include observation of clinicopathologic variables for women with hormone receptor-positive disease and refining treatment strategies for those with triple-negative disease. “We have made improvements [with] immunotherapy, and we are refining the use of checkpoint inhibitors and trying to understand if we can expand the use of immunotherapy within and beyond triple-negative breast cancer,” Rugo said. “Are there subgroups of women with hormone receptor-positive, HER2-negative disease who benefit from the addition of immunotherapy?” Efforts to address this question include the Phase 3 KEYNOTE-756 (NCT03725059) and KEYNOTE-B49 (NCT04895358) trials, both evaluating pathologic complete response (pCR) with pembrolizumab (Keytruda).
For patients with TNBC, areas of further exploration include the balance between risk and toxicity. Identifying who will benefit most from treatment and optimal checkpoint inhibition thresholds once PCR is achieved and refining the sequencing of post-neoadjuvant therapies remain areas of unmet need in this space.
ADC: the new chemotherapy
Sacituzumab govitecan-hziy (Trodelvy) and trastuzumab deruxtecan-nxki (Enhertu) have made waves for breast cancer patients, and Rugo said that antibody drug conjugates (ADCs) may very well be the next mainstays of chemotherapy for these patients. “We have seen remarkably positive data in triple negative and hormone receptor positive disease with the Trop-2 ADC sacituzumab govitecan and striking data in HER2 positive and HER2 low.” [disease] with trastuzumab deruxtecan, only transcendental information”.
The next steps are to better understand HER2 status in the Phase 3 DESTINY-Breast06 (NCT04494425) trial and to evaluate the use of trastuzumab deruxtecan in the first-line setting in the Phase 3 DESTINY-Breast05 (NCT04622319) study. For sacituzumab govitecan, Rugo noted that front-line studies are also underway, including the phase 3 ASCENT-04 trial (NCT05382286) and the planned phase 3 Optimice-RD trial (NCT04595565).
Prevention of brain metastases
Advances in drug development have not only led to advances in the treatment of primary tumors, but have also addressed an unfortunate complication of breast cancer: brain metastases. “This is a very daunting area,” Rugo said. “You have patients with a phenomenal response [to breast cancer treatment], and have leptomeningeal disease even before they can get to surgery for locally advanced TNBC. Our goal is to try to use more effective therapies to be able to prevent these metastases.”
Overcoming disparities in cancer care around the world
Rugo concluded by noting the slow progress in resolving disparities in cancer care. “There is a global initiative to improve breast cancer outcomes, [as] most patients in the world do not have access to therapies that patients [in the United States] do,” he said, adding that the problem of access also affects close to home. “Even within the US, many patients don’t have access; They are the silent minority.” Rugo cited a patient who stopped her treatment due to financial implications for her, without seeking help.
“We need to reach our patients,” Rugo said. “We need to speak out on how to address disparities in cancer care in the United States and around the world.”