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Rucaparib maintenance improved PFS in HRD-negative advanced ovarian cancer, irrespective of baseline prognostic factors.

First-Line Rucaparib Maintenance Reduces Progression Risk Across Prognostic Subgroups in HRD– High-Grade Ovarian Cancer

Raludotatug deruxtecan showed promising clinical activity in patients with heavily pretreated, platinum-sensitive ovarian cancer.

Raludotatug Deruxtecan Shows Activity in Platinum-Sensitive Ovarian Cancer 

Relacorilant plus nab-paclitaxel improved survival in platinum-resistant ovarian cancer with a primary platinum-free interval of 1 to 6 months.

Relacorilant/Nab-Paclitaxel Is Associated With Survival Improvement in Platinum-Resistant Ovarian Cancer After Short Platinum-Free Interval

Atezolizumab plus bevacizumab and chemotherapy is active in patients with persistent or recurrent metastatic cervical cancer irrespective of PD-L1 CPS.

PD-L1 CPS Does Not Enrich the Efficacy of Atezolizumab/Bevacizumab and Chemo in Advanced Cervical Cancer

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Five Under 5: Top Oncology Videos for the Week of 6/15


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The OncFive: Top Oncology Articles for the Week of 6/15

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Andres Poveda, MD, discusses the results of the phase 3 SOLO2 trial in advanced ovarian cancer.

Dr. Poveda on the Results of the SOLO2 Trial in Ovarian Cancer

® asked breast cancer experts to highlight the research and discussions they’re most excited to see presented at the meeting.

Yara Abdou, MD, an assistant professor of medicine in the Division of Oncology in the Department of Medicine at the University of North Carolina (UNC) School of Medicine-Chapel Hill; as well as the Breast Cancer Clinical Trial Program leader at the UNC Lineberger Comprehensive Cancer Center

Adam M, Brufsky, MD, PhD, a professor of medicine and associate chief of the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine; as well as co-director of the Comprehensive Breast Cancer Center, associate director of Clinical Investigation, and medical director of the Magee-Women’s Cancer Program at the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania

Neil M. Iyengar, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center in New York, New York

Alexis LeVee, MD, chief fellow of Hematology & Medical Oncology at City of Hope in Duarte, California

Bora Lim, MD, an associate professor and chief of the Section of Translational Breast Cancer Research in the Department of Breast Medical Oncology in the Division of Cancer Medicine, as well as director of Translational Research in the Department of The Morgan Welch IBC Research Program and Clinic in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center in Houston

Jane L. Meisel, MD, a professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology, as well as a professor in the Department of Gynecology & Obstetrics at Emory University School of Medicine, Winship Cancer Institute, in Atlanta, Georgia

Barbara Pistilli, MD, chair of the Breast Cancer Unit at Gustave Roussy in Villejuif, France

Sarah Sammons, MD, the associate director of the Metastatic Breast Cancer Program at Dana-Farber Cancer Institute (DFCI) in Boston, Massachusetts; as well as an assistant professor of medicine at Harvard Medical School

Paolo Tarantino, MD, PhD, a clinical fellow at DFCI

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women’s Cancers at DFCI; as well as an assistant professor of medicine at Harvard Medical School

From phase 3 data that have been teased in the news to abstracts that will add to discussions regarding shifting standards of care (SOCs), here’s what made these experts’ lists:

Abstract 1015: Treatment rechallenge after trastuzumab-deruxtecan–related interstitial lung disease: A multi-institution cohort study.

: There’s a study evaluating rechallenge of fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] after grade 1 interstitial lung disease [ILD] and how patients respond after being rechallenged. A lot of these data will be interesting to try to improve outcomes for patients, both by minimizing toxicity and by better personalizing our therapies.

: This study is exciting because T-DXd is one of the most powerful drugs in our arsenal—and ILD has been its biggest barrier. Understanding whether we can safely rechallenge patients opens the door to reclaiming a highly effective therapy for those who need it most.

Abstract 1019: Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from the phase II OptiTROP-Breast05 study.

: [Sacituzumab tirumotecan (formerly SKB264/MK-2870)]—a cousin of sacituzumab govitecan-hziy [Trodelvy]—is interesting, [and this trial] provides new opportunity to compare and learn about differences between antibody-drug conjugates [ADCs].

Abstract 1007: Phase III of oral paclitaxel (DHP107) vs intravenous paclitaxel in HER2-negative recurrent or metastatic breast cancer (mBC): Primary analysis of a multinational optimal trial (NCT03315364).

: I have been interested in various forms of oral paclitaxel, and this [trial] will certainly open a new era of oral paclitaxel, if positive.

Abstract LBA1000: Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study.

: It will be interesting to see if the PROTAC will perform as well as fulvestrant [(Faslodex) in this population].

: The phase 3 VERITAC-2 trial [NCT05654623] is a study investigating vepdegestrant, an estrogen receptor [ER] degrader…vs fulvestrant in patients who received 1 or 2 prior lines of endocrine therapy. This will be the first presentation of results for this study, [and we will see] how vepdegestrant compares with fulvestrant in terms of progression-free survival [PFS] in these patients. If this is a positive study, which we'll find out about at ASCO, it’s possible that [vepdegestrant] could become a new option for patients with ER-positive metastatic disease. There's so much excitement in this area about how to extend endocrine sensitivity, especially with agents that are well tolerated and effective. Seeing the results of this trial will maybe help push us further in that direction.

Abstract LBA109: Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study.

: [The phase 3] ASCENT-04 trial [NCT05382286] is investigating the combination of sacituzumab govitecan-hziy [Trodelvy]—a TROP-2–directed antibody-drug conjugate [ADC]—in combination with pembrolizumab [Keytruda] compared with chemotherapy of physician’s choice plus pembrolizumab for patients who have metastatic triple-negative breast cancer that’s also PD-L1 positive. [These patients are] getting treated in the first-line setting. We’ve seen a news release from this trial, which has told us that sacituzumab govitecan plus pembrolizumab did 

lead to an improvement in progression-free survival [PFS]

 compared with chemotherapy plus pembrolizumab.

 We’re hoping that will become a new first-line option for our patients. We’ve desperately been wanting to improve outcomes for metastatic triple-negative disease, so this could be a really nice improvement for patients in the early-[line] setting.

: This study is going to be interesting for a couple reasons. First, we know that that triple-negative breast cancer [TNBC] is an aggressive type of breast cancer, so the therapies we're using in the up-front setting can set the tone for how the cancer will be controlled moving forward. I view that first-line treatment selection to be critical in terms of long-term outcomes for patients. Immunotherapy has improved outcomes for patients with PD-L1–positive TNBC in the metastatic setting, but it can be a challenging regimen. Chemotherapy plus pembrolizumab is associated with several toxicities, both immune-related toxicities, as well as chemotherapy-related toxicities.

Sacituzumab govitecan is an ADC that is also [associated with] toxicities, but it is generally better tolerated than standard chemotherapy. If we have a better tolerated and more effective regimen with sacituzumab govitecan plus pembrolizumab, that would be practice changing. I'm looking forward to seeing the data to see what the numbers look like, what the magnitude of benefit is, and [to keep] an eye out for the toxicities, because it would be a win for our patients if we can use a more effective regimen that is better tolerated in the first-line setting.

: All my patients who are on this study are doing really well. I look forward to seeing the first waves of ADC plus immuno-oncology data in breast cancers.

: The ASCENT-04 study is a landmark moment—bringing ADCs like sacituzumab govitecan into the first-line setting is a bold leap forward for TNBC. It’s thrilling to see precision-engineered therapies replacing blunt chemotherapy as the new standard for the most aggressive breast cancers.

: This will be the first time that this study has reported out. Knowing how helpful sacituzumab govitecan is for metastatic TNBC in later lines of therapy makes people excited about the potential for using this [agent] closer to the first presentation of disease. And this could be [a treatment] that moves into the first-line setting if the study results are positive.

: This study included patients with TNBC who had a [PD-L1] combined positive score score of at least 10, who today are likely to receive pembrolizumab plus chemotherapy as first-line treatment.

 This study is likely to change our practice in the near future in patients with TNBC, for whom we urgently need to have new, more effective treatment options.

: This trial will likely be practice changing if the PFS [benefit] with sacituzumab govitecan/pembrolizumab exceeds [that with] the standard-of-care [SOC] therapy by a substantial and clinically significant amount.

Abstract LBA4: Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent 

 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial.

: [The phase 3] SERENA-6 trial [NCT04964934] is exciting because it’s challenging the historic paradigm of how we manage metastatic breast cancer in general. In metastatic breast cancer, we treat patients with a regimen that we know to be the most successful based on clinical trials, and we wait to change their therapy until the disease has developed resistance enough to form new tumors on scans.

SERENA-6, for the first time in a phase 3 registrational capacity, is trying to intervene on the cancer cells before we see radiographic progression, when we see that [patients] are developing mutations of resistance in the blood. This trial is in patients with metastatic estrogen receptor [ER]–positive, HER2-negative breast cancer [who had received a] first-line aromatase inhibitor [AI] and a CDK4/6 inhibitor for at least 6 months [and had undergone] blood testing to look for the emergence of 

 mutations, which denote resistance to AIs. If those patients developed an 

 mutation and still did not have progression on their scans, then they were randomly assigned to either continue their CDK4/6 inhibitor with the AI, which would be the SOC in current clinical practice, or—based on molecular emergence of an 

 mutation—switch early to camizestrant, which is an oral selective estrogen receptor degrader that targets ESR1. [in combination with a CDK4/6 inhibitor].

Can we prolong the PFS if we intervene early in the resistance [development], rather than waiting for [patients] to have disease progression on scans? PFS is the primary end point. We’re all going to want to make sure that not only PFS, but also time to second progression and potentially overall survival [OS], are improved by early switch to this type of strategy. For my patients, one of the best quality of life times that they have in their disease is their time receiving a CDK4/6 inhibitor. I’m hoping to extend the amount of time that patients can stay on their CDK4/6 inhibitor for as long as possible, because after that, we move into cytotoxic and targeted therapies that have more toxicity. [SERENA-6], if positive, is going to open the way for new trial designs and is really of value.

: There’s going to be a very cool breast cancer abstract in the plenary session. We [typically] treat patients [with ER-positive breast cancer] in the first-line setting with CDK4/6 inhibitors, and then in the second-line setting with other agents after progression. However, SERENA-6 uses a different approach, one that was derived from a prior phase 3 trial called PADA-1 [NCT03079011], where, instead of waiting for disease progression before moving to second-line treatment for hormone receptor [HR]–positive metastatic breast cancer, you switch treatment upon emergence on circulating tumor DNA [ctDNA] of 

 mutations. Approximately 40% of patients have an emergence of 

We’ll see more data from PADA-1 at the 2025 ESMO Breast Cancer Congress before ASCO, but in the SERENA-6 trial, 

, apparently switching to camizestrant upon emergence of an 

 mutation, maintaining treatment with a CDK4/6 inhibitor, led to a significant PFS advantage.

 It will be very important to look at the magnitude of benefit from this trial, because we want to understand whether a strategy of monitoring patients with ctDNA assays every 3 months in the absence of progression is advantageous in long-term outcomes, [such as] OS. It will be an important moment to see the benefit of a new drug, camizestrant, but also to understand this new paradigm of following patients with ctDNA [testing] in the absence of progression. [These data could help us] see if switching treatment is advantageous for the most prevalent category of patients we see in the clinic, which is those with metastatic HR-positive breast cancer.

: The key question with trials with this type of design is: If there's a PFS benefit with this approach, is that simply because of lead time bias, or are we truly altering and improving long-term outcomes like OS by changing therapy based upon the emergence of a resistance mutation? I'll be looking at these data with an eye to see whether there is a contribution of lead time bias. If we see a significant magnitude of PFS benefit, I think that makes lead time bias less likely. Ultimately, we will need long-term data like OS, which we received from PADA-1 before SERENA-6, to determine whether this approach of changing therapy based on emerging resistance mutations is a more effective approach than waiting for radiographic or clinical progression.

: The SERENA-6 trial is a powerful glimpse into the future of precision oncology, where we don’t just react to cancer progression, we anticipate it. Using ctDNA to guide early intervention with camizestrant represents a bold, modern shift toward truly personalized, proactive care in HR-positive/HER2-negative breast cancer.

: This is a trial asking 2 important questions. Can we detect 

 mutations early in patients receiving first-line therapy for metastatic ER-positive breast cancer [who are] doing well? And if we find those 

 mutations, can we change the course of [the disease] trajectory by switching treatment prior to seeing progression on scans? This is the first time that these results will be presented, and [they] will begin to show us [whether] there is value to checking serial ctDNA in patients who are doing well on first-line therapy. Then, if we find [a mutation], is it appropriate to switch treatment before we see progression of disease on scans? [We are], for the first time, evaluating a molecular mechanism of detecting recurrence and intervening in a patient’s treatment course. It will be interesting to see what the results of this study show and to see if they could change treatment.

: If there is a substantial and clinically significant improvement in PFS with this strategy of change to an oral selective estrogen receptor degrader before clinical progression, this will be the first demonstration [in any solid tumor] that treatment on the basis of molecular progression results in a clinically significant positive outcome. It will potentially be practice changing.

Abstract LBA1008: Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09.

: We are very excited to finally see the results of [the phase 3] DESTINY-Breast09 trial [NCT04784715], which is challenging the historical [SOC] first-line therapy in HER2-positive metastatic breast cancer that we’ve been using for over a decade now, which is a taxane with trastuzumab [Herceptin] and pertuzumab [Perjeta; THP]. DESTINY-Breast09 is a phase 3 trial that is investigating first-line therapy for these patients with 3 different arms: T-DXd, T-DXd with pertuzumab, or the control arm, which is the historical SOC of THP.

 [according to] a news release, but we really need to see the results.

 They will lead to a lot of open questions in this patient population as to whether T-DXd with or without pertuzumab is superior in terms of PFS, which is the primary endpoint. How long are patients staying on this drug? In this trial, patients receive T-DXd indefinitely until progression or toxicity. There are open questions as to how long we need to continue T-DXd, how well our patients will tolerate T-DXd, and whether it’s truly a superior first-line therapy. Another [finding] I am very interested in seeing is whether we could potentially even consider curing more patients with HER2-positive metastatic breast cancer if we use more effective first-line therapies.

: We’ve already seen a news release from this trial, which has told us that at the time of an interim analysis, the combination of T-DXd plus pertuzumab led to a significant improvement in PFS. We’re all excited to see whether that could become a new SOC option for our patients.

: It will be important to dissect these data, because the current SOC, the phase 3 CLEOPATRA trial [NCT00567190] regimen, [is one] we have been using for a long time. We have long-term follow-up on the CLEOPATRA data. T-DXd is an effective treatment for HER2-positive and HER2-low breast cancer. The main question I'll have in my mind when reviewing the DESTINY-Breast09 data is: What is the magnitude of benefit [with T-DXd plus pertuzumab] over THP, particularly in terms of duration of response and PFS? This is an interim report, so we won't have long-term data to compare with [those from] CLEOPATRA.

The challenge in integrating the DESTINY-Breast09 data—if we will want to integrate [them]—is that the CLEOPATRA regimen offers a maintenance setting where we can withdraw the chemotherapy if a patient has a favorable response and maintain that response with just the antibody therapy, trastuzumab and pertuzumab. We've seen results from the phase 3 PATINA trial [NCT02947685], which indicates that adding the CDK4/6 inhibitor palbociclib [Ibrance] to hormone therapy during that maintenance period further extends PFS.

From a QOL standpoint, it is attractive to start with an induction period of chemotherapy based on the CLEOPATRA trial, maintain the response—if it's a good response—with the anti-HER2 antibodies trastuzumab and pertuzumab, and add in hormone therapy and palbociclib. DESTINY-Breast09 was designed like CLEOPATRA, so a maintenance period was not included. The question will be: Is the magnitude of benefit in DESTINY-Breast09 large enough to replace the CLEOPATRA regimen in the first-line setting and forego that maintenance period, which has a high QOL associated with it? Or are we still going to be using the CLEOPATRA regimen in the first-line setting, so we can use that maintenance period, as we already know that T-DXd is effective in the second-line setting and beyond?

: T-DXd is an exciting drug. It was first shown to be effective as later-line, HER2- directed therapy for patients with metastatic HER2-positive breast cancer. Then it eventually moved up [to become] the second-line SOC for these patients and has since also been shown to be effective for patients with HER2-low and even HER2-ultralow metastatic disease. Lots of patients are benefiting from this drug, but DESTINY-Breast09 is asking the question: In patients who are truly HER2 positive, might [T-DXd] be even more useful than the current SOC for patients with a new diagnosis of metastatic disease? This trial investigating how T-DXd performs in the frontline setting is a study that everyone has been eagerly awaiting, because if this is a positive study, we may be able to move this drug into the frontline setting for patients with HER2-positive metastatic disease, thus changing the SOC.

: This is a huge study that included 1157 patients across different countries in the world.

This may change our clinical practice and the treatment algorithm for patients with HER2-positive advanced breast cancer. It is likely that we are going to advance treatment with T-DXd into the first-line setting. The question thereafter will be: Can we keep these patients on this treatment for the long term? One of the major issues we have to face is to understand the optimal maintenance therapy we can use in patients receiving T-DXd in the first-line setting who cannot continue the treatment until progression.

: This trial will likely be practice changing if the PFS with T-DXd exceeds [that with] the SOC therapy by a substantial and clinically significant amount.

Iyengar: We'll see interesting data with regard to modifiable risk factors for breast and other cancers. We will see a couple of studies looking at various cancer risk factors, both hereditary and environmental, including obesity as a risk factor for developing breast and other cancers. We are going to see 2 studies that will be presented, looking at the use of weight loss therapy in patients both with and without diabetes, and their effect on breast cancer risk.

One of the studies, [abstract 10507], is based on a large dataset [with an] interesting trial design. The investigators emulated a clinical trial using an observational dataset to look at the effect of GLP-1 receptor agonists on the development of obesity-related cancers in patients with diabetes. That will add to the growing literature looking at the effect of these novel weight loss therapies on obesity-associated cancers. [Then, abstract 10508] is a target trial emulation study looking at the effect of GLP-1 receptor agonists on cancer risk. This includes patients with diabetes, as well as patients without diabetes who use the drugs purely for the weight loss indication.

These 2 studies are going to be particularly informative because we've only seen small datasets so far in the post-diagnosis setting [regarding] the degree of weight loss with GLP-1 agonists in patients diagnosed with cancer. In the risk setting, we've seen a couple observational studies looking at large national databases that have shown that the use of weight loss drugs—particularly GLP-1 agonists—is associated with a lower incidence of developing obesity-associated cancers. However, those studies have really been isolated to patients with diabetes and patients who've been prescribed these drugs for diabetes treatment. A big question is: Now that the GLP-1 receptor agonists have an indication for weight loss independent of diabetes and are being used in patients without diabetes, do the drugs still have an effect on lowering the risk of developing obesity-associated cancers?

There are at least 13 obesity-associated cancers, including breast cancer. If these drugs do lower the risk of [developing] these 13 cancers independent of diabetes, this would be a potentially effective prevention strategy. The next steps would be to validate these observational findings in a prospective manner, and then address a lot of the disparities that exist with regard to access to these drugs, the cost of these drugs, etc. However, the first step is really looking at the association of these drugs on cancer risk.

Abstract 501: Predicting pathologic complete response (pCR) from clinicopathologic variables and HER2DX genomic test in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): Secondary results from the EA1181/CompassHER2 pCR trial.

: One trial I’ve been really looking forward to is the [phase 2] CompassHER2-pCR trial [NCT04266249]. For patients who get treated in the early-stage setting for HER2-positive disease, the standard, at least in the United States, is usually to give a THP for 6 cycles. However, that therapy is associated with significant toxicities, so we’ve always wondered: Could we just give a taxane with trastuzumab and pertuzumab for 12 weeks, and then if [the patients achieve] a pathologic complete response [pCR], just continue the trastuzumab/pertuzumab antibodies to complete a year? [We though that might be] sufficient therapy for them because they got a pCR. Smaller studies have shown us that THP can result in very good pCR rates, but [CompassHER2-pCR is a] large cooperative group trial that will be important to see. [The investigators are also examining] a novel biomarker, HER2DX, and associating it with the pCRs in this trial. It will be interesting to see whether the HER2DX assay does well in predicting pCR.

Trodelvy plus Keytruda demonstrates a statistically significant and clinically meaningful improvement in progression-free survival in patients with previously untreated PD-L1+ metastatic triple-negative breast cancer. News Release. Gilead. April 21, 2025. Accessed May 13, 2025. https://www.gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-trip

Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 Phase III trial. News release. AstraZeneca. February 26, 2025. Accessed May 13, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-improved-pfs-in-1l-hr-breast-cancer.html

Enhertu plus pertuzumab demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival vs. THP as 1st-line therapy for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. April 21, 2025. Accessed May 13, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-combination-improved-pfs-in-1l-her-positive-mbc.html

To prepare for the 2025 ASCO Annual Meeting, breast cancer experts share the abstracts and discussions they’re most excited to see at the meeting.

Clinical

Conference

Breast Cancer Experts Bookmark Top Abstracts to Watch at the 2025 ASCO Annual Meeting

In The incorporation of CDK4/6 inhibitors into the adjuvant treatment of patients with hormone receptor (HR)–positive, HER2-negative early-stage breast cancer has introduced an additional strategy to reduce recurrence risk following standard multimodal therapy, according to Arielle Heeke, MD, who noted that the recent addition of ribociclib (Kisqali) to the adjuvant treatment arsenal has broadened the applicability of this approach.

FDA approved abemaciclib (Verzenio) in combination with endocrine therapy

 for the treatment of patients with HR-positive, HER2-negative, early-stage breast cancer at high risk of recurrence and a Ki67 score of 20% or greater based on results from the phase 3 monarchE trial (NCT03155997).

 in March removed the Ki-67 score requirement for patient selection.

FDA approved ribociclib plus an aromatase inhibitor (AI)

for the treatment of patients with HR-positive, HER2-negative stage II/III early breast cancer at high risk of recurrence, based on data from the phase 3 NATALEE (NCT03701334).

“CDK4/6 inhibitors can be prescribed to patients with stage II or [higher] breast cancer, and the data are strong for both [abemaciclib and ribociclib]. [Accordingly, selecting between these agents] can be based on patient and/or provider preference,” Heeke said during an interview with 

® following a State of the Science Summit™ on breast cancers. “Over time, [however], we will probably lean into [using] ribociclib in the non-metastatic setting.”

In the interview, Heeke highlighted the role of CDK4/6 inhibitors in the HR-positive, HER2-negative, early-stage breast cancer treatment paradigm; key clinical considerations when choosing between abemaciclib and ribociclib; and how the FDA approval of the PARP inhibitor olaparib (Lynparza) has improved the treatment arsenal in this space.

Heeke is a clinical associate professor in the Department of Hematology and Oncology at Wake Forest University School of Medicine and a physician at Atrium Health Levine Cancer Institute in North Carolina.

: How have CDK4/6 inhibitors in the adjuvant setting changed the treatment paradigm for patients with HR-positive, HER2-negative early-stage breast cancer?

 [This is] a tough diagnosis to get, [although] patients [with this disease] have [many] treatment options. There’s potentially chemotherapy, obviously surgery and radiation, endocrine therapy for 5 to 10 years, ovarian suppression, and now CDK4/6 inhibitors. We are using them a lot because they're helpful, especially when you have somebody that, at the end of all that other [treatment], still has a high risk of recurrence. [For example, if they have a risk of recurrence of] 30%, and they're interested in [receiving CDK4/6 inhibitors,] that could reduce approximately 7% of their risk. However, it doesn't take the risk of recurrence down to 0%, which is the tough thing. We wish we could promise people that, but a 30% or even 20% risk of recurrence after completion of their other therapies is uncomfortably high. Therefore, if they can get it down closer to 10%, it's often worth it to the patient.

We're lucky to have 2 [CDK 4/6 inhibitors] now. Abemaciclib is helpful because it's only [taken for] 2 years. The data [showing its efficacy] are strong, but the control arms are a little different. Ribociclib is generally a little easier to tolerate. In practice, I recommend CDK4/6 inhibitors for patients with lymph node–positive disease. The NATALEE study has certainly challenged that a little bit, because it's available for lymph node–negative disease as well. [That study has] shown that all subgroups were benefiting similarly from the addition of ribociclib to [endocrine therapy], which speaks to how we don't know exactly [which] patients need the therapy. It could be in both groups. Personally, I hope that circulating tumor DNA will help us better select [the appropriate patient population].

What are some key clinical considerations when selecting CDK4/6 inhibitors for your patients?

When ribociclib was FDA approved [for this indication], I was still more fond of the abemaciclib, just because the absolute benefit seemed greater. We had gotten comfortable with patients taking it already and although it wasn't necessarily the most fun [treatment], patients were [taking it] and getting through the 2 years [of treatment]. With it, I wasn't admitting people to the hospital because of horrible diarrhea or any [adverse effects] like that. It was a quality-of-life damper, but the patients were getting through it okay. Now that I've [come to know] the data a little bit better between monarchE and NATALEE and have a better understanding of the calculated differences in the experimental and control arms, with patients in the control arm on NATALEE doing better, I'm feeling much more comfortable leaning into ribociclib. The only caveat there is the 3-year treatment duration—I haven't had that experience of trying to keep somebody on therapy for the full 3 years. However, in terms of tolerance of the patients that I've put on the ribociclib in the adjuvant setting, they seem to tolerate it better than when we put them on adjuvant abemaciclib. In the metastatic setting, the 600 mg dose of ribociclib is challenging. People do struggle with fatigue and cytopenias, but the 400 mg [dose] is generally well tolerated.

How has the addition of olaparib (Lynparza) to the treatment toolbox in 

-mutated, high-risk early breast cancer improved patient outcomes?

First, there aren’t that many patients with 

Arielle Heeke, MD, highlights the role of adjuvant abemaciclib and ribociclib in patients with HR-positive, HER2-negative, early breast cancer.

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