Stage Is Set for Exploring TNBC, HER2-Positive Settings at 38th Annual CFS

Tiffany A. Traina, MD

Delivering evidence-based state-of-the art cancer care in the management of hematologic and solid malignancies is the mainstay of the 38th Annual CFS®: Innovative Cancer Therapy for Tomorrow conference taking place virtually November 4 through 6, 2020. Presentations that provide critical knowledge and competencies for myeloproliferative neoplasms, lymphomas, leukemias, and multiple myeloma will be offered on the first day, followed by sessions covering genitourinary malignancies.

The second day focuses on gynecologic oncology, der-matologic cancers, and breast cancer. Day 3 addresses lung cancer; head, neck, and thyroid cancers; gastro-intestinal cancers; and other challenging tumor types including brain and neuroendocrine tumors.

Tiffany A. Traina, MD, co-chair of the breast cancer session, provided an overview of the day’s program, noting that 2 clinical settings in breast cancer are enjoying renewed excitement: HER2-positive disease and triple-negative breast cancer (TNBC).

Traina said the HER2-positive breast cancer space has seen 2 recent FDA-approved agents that clinicians can add to their armamentarium, both of which demon-strate impressive efficacy results. With the approvals of fam-trastuzumab deruxtecan-nxki (Enhertu) and tucatinib (Tukysa), the question becomes how best to use these agents for optimal patient benefit.

“Attending the virtual meeting is a fantastic opportu-nity to hear from experts in the field about how they use these data [and agents] in their daily practice,” Traina, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, said during an interview with Targeted Therapies in Oncology. She will present “Early-Stage HER2-Positive Breast Cancer: Putting Data to Practice” during the conference.

Fam-trastuzumab deruxtecan-nxki was approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior lines of anti–HER2-based regi-mens in the metastatic setting.1 The approval is based on findings from the phase 2 DESTINY-Breast01 trial (NCT03248492).²

In that study, the agent induced a confirmed objec-tive response rate (ORR) of 60.9% according to inde-pendent central review (ICR; 95% CI, 53.4%-68.0%), including a 6.0% complete response rate and a 54.9% partial response rate. Sixty-seven patients had stable disease (36.4%), and 3 had progressive disease (1.6%). The investigators reported that ORRs were consistent across subgroups, including those with prior treatment with pertuzumab (Perjeta; 64%) and those with more than 3 prior regimens (59%).

The other new agent in this space is the oral tyrosine kinase inhibitor tucatinib. “This agent has shown prom-ising survival data in patients with brain metastases, which is a tremendous area of unmet need,” Traina said.

The FDA granted accelerated approval for tucatinib tablets in combination with trastuzumab (Herceptin)and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received 1 or more prior anti–HER2-based regimens in the metastatic setting. The approval was based on positive results from the phase 2 HER2CLIMB trial (NCT02614794), which were published in the New England Journal of Medicine.3 The application for the combination was reviewed under the FDA’s Project Orbis, an initiative of the FDA Oncology Center of Excellence in collaboration with the Australian Therapeutic Goods Administration, Health Canada, the Health Sciences Authority of Singapore, and Switzerland’s Swissmedic.

Triple-Negative Breast Cancer

The second setting of interest is the TNBC space, Traina said, which is highlighted by the approval of the antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy). The ADC is approved for the treatment of adult patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease.5 “This [agent] has offered hope and promise for patients being treated in the third line or later for TNBC,” Traina said.

Also discussing the use of ADCs in breast cancer will be Aditya Bardia, MD, MPH, assistant professor of medicine at Harvard Medical School and attending physician at Massachusetts General Hospital, both in Boston. He will present “What is the Role of Antibody-Drug Conjugates in HER2-Negative Breast Cancer?”

Traina said that TNBC tumors are heterogeneous and contain a constellation of drivers and multiple tumor groups that adds to its clinical complexity. But research is now focusing on the androgen receptor (AR) in a subset of patients with TNBC who are AR-positive.

“There is compelling evidence that the androgen pathway may deliver the next target for drug development,” Traina said, referring to a phase 2 safety and efficacy study evaluating enzalutamide (Xtandi) in this subpopulation (NCT01889238). In tumors driven by hormones, targeting the pathway rather than using chemotherapy may offer an approach with better toxicity profiles, explained Traina.

“Rather than adding this [agent] to chemotherapy, we could lead with an endocrine approach, and then at some point introduce chemotherapy down the line. It’s not unlike the way we manage an estrogen-driven cancer with targeted therapy,” Traina said. The study will determine if there is a clear subgroup of patients with TNBC who could benefit from a nonchemotherapy approach.

Expanding Use of Immunotherapy

Earlier use of immunotherapies in the frontline setting shows greater benefit than in later-line settings, Traina said. Further, moving checkpoint inhibitors into the neoadjuvant setting, and potentially the adjuvant setting, may demonstrate even more benefit.

Perhaps the biggest impact of the use of immunotherapy agents occurs when they’re combined with cytotoxic chemotherapy or radiation therapy, she added. Determining which agents to combine is the subject of ongoing research. Virtual attendees can hear a broad overview of immunotherapeutics as they are used to treat various breast tumors, presented by Heather L. McArthur, MD, MPH, medical director of breast oncology at Cedars-Sinai Medical Center in Los Angeles, California, who will also be discussing future directions in immunotherapy.

ER-Positive Disease Regarding trial results that she’s looking forward to seeing, Traina pointed out that the phase 3 PALLAS (PALbociclib CoLlaborative Adjuvant Study; NCT02513394) trial in the estrogen receptor (ER)–positive space will help to further inform clinicians.

A preplanned efficacy and futility analysis by the Independent Data Monitoring Committee determined that the trial is unlikely to show a statistically significant improvement in the primary end point of invasive disease-free survival.⁶

“The trial’s primary end point did not show an advantage of palbociclib [Ibrance] on top of endocrine therapy in the adjuvant setting,” Traina said. “It will be interesting to see these data in greater detail in order to understand the impact of [CDK 4/6 inhibitors] in early-stage disease for ER-positive breast cancer.”

PALLAS compares palbociclib plus standard adjuvant endocrine therapy with standard adjuvant endocrine therapy alone in women and men with hormone receptor–positive, HER2-negative early (stage II and III) breast cancer. In a press release, the manufacturer, Pfizer, said that no new safety signals were observed in patients receiving palbociclib.

Adapting to Virtual Meetings

Traina said that over the last few months, people have become familiar with the virtual platforms that are now a steady part of attending medical meetings.

“The high value point of this meeting is the relationships that develop between attendees and faculty,” Traina said. Features such as Live Chat, in which participants can be engaged with the meeting by connecting with colleagues and interpreting and sharing data, can improve and enhance this version of the meeting compared with previous years. “Despite the pandemic, I’m still building networks,” she said.

_References:

_{1. FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies. News release. FDA; December 20, 2019. Updated December 23, 2019. Accessed August 18, 2020. bit.ly/2tzcabv}

_{2. Krop IE, Saura C, Yamashita T, et al. [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) in subjects with HER2-positive metastatic breast cancer previously treated with T-DM1: a phase 2, multicenter, open-label study (DESTINY-Breast01). Cancer Res. 2020;80(4 suppl):GS1-03. doi:10.1158/1538-7445.SABCS19-GS1-03}

_{3. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597-609. doi:10.1056/NEJMoa1914609}

_{4. FDA approves tucatinib for patients with HER2-positive metastatic breast cancer. News release. FDA; April 17, 2020. Updated April 20, 2020. Accessed August 18, 2020. bit.ly/2YgAHil}

_{5. FDA grants accelerated approval for Immunomedics’ Trodelvy in previously-treated metastatic triple negative breast cancer. News release. Immunomedics; April 22, 2020. Accessed August 18, 2020. bit.ly/3h9zyjX}

_{6. Pfizer provides update on phase 3 PALLAS trial of Ibrance (palbociclib) plus endocrine therapy in HR+, HER2– early breast cancer. News release. Pfizer; May 29, 2020. Accessed August 18, 2020. bit.ly/3aIzo0r}