End-of-Year Wrap Up: Reflecting on Breast Cancer Updates in 2021

As the year 2021 comes to a close, CancerNetwork® reflects upon the plethora of updates that have taken place within the breast cancer space, from premenopausal patients to those with triple-negative breast cancer (TNBC), as well as those with estrogen receptor (ER)–positive disease, according to Amy Comander, MD.

Additionally, Comander shared her thoughts on what 2022 may hold for patients with breast cancer.

“[It’s] a wonderful thing to think about,” she stated. “I’m hopeful that we’re going to learn more and more about how we can deescalate treatments in some of our patients who may not need as aggressive treatments such as chemotherapy for premenopausal women. Maybe we’ll be able to understand a little bit better which patients can avoid chemotherapy. Also, we’ll learn which patients we should be escalating therapy further to help prevent recurrences and improve their outcome and chances of cure. Our field is evolving this way. It’s really exciting to see that happen.”

In part 3 of our 4-part series reflecting on 2021 updates in cancer care, CancerNetwork® sat down with Comander, co-medical director and director of breast oncology and cancer survivorship at Mass General Cancer Center, to highlight data that read out at the 2021 San Antonio Breast Cancer Symposium (SABCS) and key regulatory decisions from the FDA for patients with breast cancer.

Be sure to read part 1 of our series, wherein Yael Cohen, MD, reflected on updates in the multiple myeloma space, and part 2, which featured insights by Matthew Davids, MD, on key research in chronic lymphocytic leukemia that read out in 2021.

CancerNetwork^®: Our conversation follows this year’s SABCS. How do you see findings from the phase 3 RxPONDER trial (NCT01272037) impacting the care of premenopausal patients?¹

Comander: It’s great to start with this study because it is certainly practice changing and relevant to so many of the patients we see every single day in a breast oncology clinic. A key finding from this study is that the majority of patients with hormone receptor–positive, HER2-negative tumors with 1 to 3 positive nodes can be spared chemotherapy when we use the OncotypeDX test to help guide treatment. I should say, in the majority of postmenopausal patients, the studies show that postmenopausal women with 1 to 3 positive nodes and a recurrence score from 0 to 25 can forego chemotherapy regardless of other clinical parameters. It was really interesting to see the update on those data presented at [SABCS].

What is still tricky, however, is how we interpret the data with regard to premenopausal patients. In this study that was presented, it was demonstrated that those individuals who are premenopausal with 1 to 3 positive nodes and [with] a recurrence score result from 0 to 25 did seem to derive benefit from chemotherapy. But that does still raise many questions. Is the chemotherapy itself providing that benefit or is this benefit secondary to ovarian suppression? I will say at [SABCS], there was a very interesting debate on this exact topic. How do we interpret the RxPONDER results with regard to premenopausal women. [In] my tumor board this morning, we also debated it. This is still a question that we are going to continue to scratch our heads about with our patients since we’re trying to find the best treatment, especially for our younger women.

How do you see yourself applying these data in clinical practice?

That’s a great question, since it has already come up in clinic a few times since the meeting. Certainly with some of our patients [who have] limited nodal burden of disease and an Oncotype DX score that is low—and again, I’m referring to our premenopausal patient population—it really does lead to an interesting discussion with the patient about the data, what the RX ponder trial showed, and what we have from other studies, such as [the phase 3] MINDACT trial [NCT00433589]. [MINDACT] helped inform this decision about the potential benefit of chemotherapy. Is it the chemotherapy [that’s providing the benefit or] is it the ovarian suppression? Is it a combination of both? I’ve already had some interesting discussions with many of my patients. As we continue to follow the data, the story will evolve and we’ll be able to make more precise recommendations for our patients.

Pivoting to another study that was presented at this year’s meeting, could you highlight the updated findings of the phase 3 KEYNOTE-522 trial (NCT03036488)?²

It was exciting to see the update to the KEYNOTE-522 data. Just as a reminder, in this study approximately 1200 patients with previously untreated nonmetastatic TNBC were randomized to receive treatment with neoadjuvant pembrolizumab [Keytruda] or placebo every 3 weeks, each given with 4 cycles of paclitaxel plus carboplatin followed by 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. With further follow-up for the participants in this study, it was demonstrated that those individuals who did receive pembrolizumab had a significantly higher pathologic complete response rate than those who had the placebo. There was [also] a significant benefit in terms of event-free survival. It was exciting to see the update on these data. It certainly has very important implications in the clinic.

In July 2021, we saw the FDA approval of that KEYNOTE-522 regimen for patients with TNBC following a complete response letter that was issued in March 2021. What are the potential implications of this regulatory decision?

I was personally very excited to see that. I saw a patient in clinic yesterday, a young woman presenting with a new diagnosis of TNBC and, unfortunately, with lymph node involvement. I was able to outline my treatment plan for her, which is based on the regimen from KEYNOTE-522. It was exciting for me to tell her that this regimen was just FDA approved 5 or 6 months ago and is practice changing. [Being able] to instill hope in her regarding the power of research to find better treatments for what is a very aggressive high-risk disease [was uplifting]. My patient and her family really felt inspired and hopeful after learning about the advances that we’ve seen in treatment of TNBC just in the past few years.

Shifting to a different patient population, what kind of updates have we seen this year in the ER-positive disease space?

The majority of the patients [with breast cancer who] we care for have a diagnosis of ER-positive disease, [including] those individuals who develop recurrence or who have advanced estrogen-sensitive breast cancer. We’re always exploring new therapies for this patient population. Another really exciting study that was presented at the SABCS was the pivotal phase 3 EMERALD trial [NCT037789310], which studied the selective ER degrader elacestrant (RAD-1901).³ But it showed that this medication significantly showed benefit in terms of progression-free survival [PFS] compared with a different form of endocrine therapy, which was up to the physicians choice in that study. It was amazing to see this significant benefit and improvement in PFS in this group receiving this novel drug that’s an oral agent that is well tolerated. It’s just amazing to have another option for our patients with advanced estrogen sensitive breast cancer.

How are you working to incorporate these different findings into daily clinical practice?

There were many exciting presentations at the meeting this year. One of the areas that I’m also interested in is survivorship care and how we can optimize care for our breast cancer survivors. There was a great discussion with numerous abstracts focused on novel areas of cancer survivorship ranging from fertility preservation to diet and exercise interventions. This is an area that’s wide open for further innovation in the next few years. I’m excited to see the results from those studies.

In regard to other updates that we have seen over the course of 2021, we saw the full approval of sacituzumab govitecan (Trodelvy) for TNBC. How has that indication impacted the treatment landscape?

As we discussed, TNBC is unfortunately often aggressive and our treatment options have been quite limited to various types of chemotherapy agents. The advent of the [phase 3] ASCENT trial [NCT02574455] showed us that the drug sacituzumab govitecan can be effective in our patients with TNBC who have already received at least 2 lines of prior therapy.⁴ In my own clinic, I have many women who did meet those criteria and who were looking for their next treatment option. The drug is, for the most part, well tolerated. Certainly, individuals may experience nausea, diarrhea, and blood count issues, but for the most part, it has been well tolerated. Some of my patients have been on it for many months. It has been exciting to have another tool to treat this very aggressive subtype of breast cancer.

Reflecting back on 2021, do you have any end-of-year takeaways?

I would like to give a shout out to all of the amazing clinical researchers and investigators and of course, patient volunteers who participated in studies over these past challenging 20 months. Going through getting a diagnosis of cancer at any time is certainly challenging and disruptive. But to be diagnosed with cancer and go through treatment during [the COVID-19] pandemic has been an immense challenge. I’m just amazed to see all the progress we’ve made for our patients over this very challenging time.

References

1. Kalinsky KM, Barlow WE, Graloe JR, et al. Updated results from a phase 3 randomized clinical trial in participants (pts) with 1-3 positive lymph nodes (LN), hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25 randomized to endocrine therapy (ET) +/- chemotherapy (CT): SWOG S1007 (RxPONDER). Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS2-07.
2. Schmid P, Cortes J, Dent R, et al. KEYNOTE-522 study of neoadjuvant pembrolizumab + chemotherapy vs placebo + chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC: Event-free survival sensitivity and subgroup analyses. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.
3. Bardia A, Neven P, Streich G, et al. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS2-02.
4. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384:1529-1541. doi:10.1056/NEJMoa2028485