The landscape of gynecologic oncology is rapidly evolving, driven by scientific discovery, surgical innovation, and a growing emphasis on multidisciplinary care. To bring these advances directly to practicing clinicians, 

From Discovery to Delivery: Charting Progress in Gynecologic Oncology

, hosted by Ursula A. Matulonis, MD, chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School in Boston, Massachusetts.

The series aims to provide in-depth conversations with leading experts on emerging science, therapeutic innovation, and evolving treatment strategies across the spectrum of gynecologic cancers. In the inaugural episode, Matulonis welcomes Taymaa May, MD, MSc, director of Ovarian Cancer Surgery at Brigham and Women’s Hospital and member of the obstetric faculty at Harvard Medical School in Boston, Massachusetts, to explore what’s new in gynecologic cancer surgery.

Opening the conversation, Matulonis set the tone for the series. “Surgery is a bedrock modality of treatment for [patients with] gynecologic cancers,” she said. “It felt very appropriate to begin this series by focusing on the innovations transforming how we operate and how patients recover.”

Matulonis introduced her guest by highlighting May’s extensive training and reputation for surgical precision and compassionate care. May completed her medical degree at McGill University, residency in obstetrics and gynecology at the University of Toronto, and fellowship in gynecologic oncology at Brigham and Women’s Hospital, where the two first met. After beginning her academic career at Princess Margaret Cancer Centre in Toronto, May returned to Boston in 2023 to lead ovarian cancer surgery at Brigham and Women’s Hospital.

“Surgery is a cornerstone of treatment and often [is] the first therapeutic step for patients with gynecologic cancers,” May said. “Roughly 80% of patients will meet a surgeon early in their cancer journey, making the surgical encounter foundational for diagnosis, treatment planning, and long-term outcomes.”

Reflecting on the major advances over the past 2 decades, May described minimally invasive surgery as one of the most transformative developments in the field. “The laparoscopic and robotic platforms have completely reshaped how we deliver surgical care,” she explained. “We can now perform the same comprehensive staging and complex procedures through smaller incisions, offering patients faster recovery and shorter hospital stays without compromising cancer outcomes.”

Beyond shorter recovery times, these techniques have also improved precision in oncologic staging and reduced complications. Building on these advances, May highlighted another leap forward: sentinel lymph node mapping.

“Lymph node mapping allows us to identify and remove only those lymph nodes most likely to harbor disease,” she said. Using infrared imaging and targeted dyes, surgeons can visualize lymphatic drainage in real time during the procedure. “This means we can stage patients with the same accuracy but with far less morbidity. The risk of complications like lower-extremity lymphedema has dramatically declined.”

Matulonis underscored the clinical impact. “That is a huge advantage,” she said. “Lymphedema was such a significant problem for so many patients in the past. Sentinel node mapping is truly a patient-centered advance.”

The critical role of the gynecologic oncologist

As the conversation turned toward care delivery, Matulonis emphasized a key message for clinicians and patients alike: the importance of being treated by a gynecologic oncology specialist.

May agreed, noting, “Multiple national studies have shown that surgical and survival outcomes are significantly better when patients are treated by a gynecologic oncologist. The expertise required for these procedures, and the nuanced decisions about whether surgery, chemotherapy, or a combination is most appropriate, really demands specialized training.”

She continued, “Surgery is not just a technical act. The decision-making process, the oncologic judgment, is central to the treatment plan. It’s about asking, ‘What is the optimal and most beneficial approach for this patient, given their tumor biology, stage, and overall health?’ That’s what guides us.”

Matulonis added that this expertise is especially critical when managing advanced gynecologic cancers, where determining whether a patient should receive upfront surgery or neoadjuvant chemotherapy can directly influence survival and quality of life.

Ovarian cancer remains one of the most challenging malignancies in gynecologic oncology, often diagnosed at an advanced stage. May discussed the evolution of multivisceral resection techniques and the integration of new tools designed to enhance safety and precision.

“One of the key innovations we now use is fluorescence angiography,” she explained. “When we resect a segment of bowel during debulking surgery, we need to ensure the newly joined sections are well perfused to prevent leaks or complications. By injecting a fluorescent dye and visualizing blood flow in real time, we can objectively assess perfusion in less than a minute. It’s a small step that has had a major impact on outcomes.”

Matulonis remarked that such innovations address some of the most serious potential complications in major abdominal surgery. “That’s a very significant advance,” she said. “It’s incredible how technology can now guide us intraoperatively to prevent problems that once carried major morbidity.”

Preserving fertility in cervical cancer surgery

The discussion then shifted to cervical cancer, particularly among younger patients, where preserving fertility remains a vital consideration. May described the development and refinement of the radical trachelectomy, a procedure that removes the cervix and surrounding tissues while preserving the uterus.

“This approach allows us to achieve the same oncologic outcomes as a hysterectomy for select early-stage patients, while maintaining the potential for future pregnancy,” May explained. “We remove the cervix and lymph nodes through either a vaginal or minimally invasive approach and then reconstruct the anatomy to allow for fertility preservation.”

She cited her team’s recent study comparing outcomes between robotic and vaginal trachelectomy in approximately 200 patients, showing equivalent safety and survival outcomes.

 “For carefully selected patients, minimally invasive trachelectomy is a safe and effective fertility-sparing option,” she concluded.

Matulonis noted how impactful these results are for younger patients facing cancer diagnoses. “Cervical cancer is often diagnosed in people who are still of childbearing age,” she said. “These fertility-sparing advances can make an extraordinary difference in their lives.”

Personalizing surgery in advanced ovarian cancer

In addition to her surgical research, May has contributed extensively to the data guiding treatment sequencing in advanced ovarian cancer. Matulonis highlighted a retrospective study led by May that compared outcomes among nearly 300 patients with 

-mutated ovarian cancer, evaluating whether primary debulking surgery or neoadjuvant chemotherapy followed by interval surgery led to better survival outcomes.

May explained, “Ovarian cancer treatment is multifaceted. We have 2 cornerstone modalities, systemic chemotherapy and cytoreductive surgery, but determining which to do first must be individualized. Every patient’s disease distribution and tumor biology are different.”

 mutations who underwent primary surgery followed by chemotherapy had improved overall survival compared with those treated with neoadjuvant chemotherapy first.

“This highlights the importance of personalizing care,” May said. “Even among patients with similar stages of disease, surgical operability and tumor biology can vary greatly. A tailored approach that integrates molecular data and clinical assessment is essential.”

Matulonis applauded this precision-based framework. “That’s such an important point: the need for individualized decision-making and for multidisciplinary review of each patient’s case.”

At Brigham and Women’s Hospital, May leads a weekly tumor board dedicated to reviewing imaging, pathology, and genetic findings to determine optimal therapeutic sequencing. “These decisions should always be made in collaboration with a gynecologic oncologist,” Matulonis added. “That’s where outcomes truly improve.”

Integrating innovation and team-based care

As the episode concluded, May reflected on how technology and data are transforming surgical practice. “We’re using innovative tools not only in the operating room but also in preoperative planning and recovery,” she said. “Objective risk algorithms, imaging-based assessment, and biomarkers help us predict surgical outcomes and guide patient optimization.”

Importantly, she noted that recovery itself is a critical component of treatment success. “Early and complete recovery allows patients to start adjuvant therapy, [be it] chemotherapy or radiation, on schedule, which is vital for improving survival,” May emphasized. “That’s why collaboration among surgeons, medical oncologists, anesthesiologists, and nursing teams is so essential.”

Matulonis agreed, highlighting how the field has become increasingly multidisciplinary and data-driven. “We’re now integrating genomics, surgical innovation, and systemic therapies in ways that were unimaginable a decade ago,” she said. “It’s an incredibly exciting time to be in gynecologic oncology.”

In closing, Matulonis thanked May for joining the first episode of the series and for her leadership in advancing the surgical management of gynecologic cancers. “Your insights into innovation, fertility preservation, and individualized care have set a wonderful tone for this new podcast,” she said.

May expressed her appreciation: “It’s been an honor to discuss these advances with you. The future of gynecologic oncology is bright, and continuing to share knowledge across institutions and specialties is how we’ll keep improving outcomes for our patients.”

As this series continues, upcoming episodes will explore evolving frontiers in immunotherapy, targeted therapy, and clinical trial design in gynecologic cancers, all with the goal of equipping oncologists with the most current, clinically relevant information to enhance patient care.

With expert-driven discussions at the forefront, the series promises to be an invaluable resource for clinicians seeking to stay abreast of the fast-changing landscape of gynecologic oncology.

Nica A, Benseler A, Parbhakar A, et al. Robotic versus vaginal radical trachelectomy for reproductive-aged patients with early-stage cervical carcinoma: a multi-center cohort study. 

. 2024;185:95-100. doi:10.1016/j.ygyno.2024.02.018

Kim SR, Parbhakar A, Li X, Bernardini MQ, Hogen L, May T. Primary cytoreductive surgery compared with neoadjuvant chemotherapy in patients with BRCA mutated advanced high grade serous ovarian cancer: 10 year survival analysis. 

. 2024;34(6):879-885. doi:10.1136/ijgc-2023-005065

Articles

The field of gynecologic oncology is advancing rapidly, with innovations in surgery and multidisciplinary care. A new podcast series, hosted by Dr. Ursula A. Matulonis, aims to disseminate these developments to clinicians. The inaugural episode features Dr. Taymaa May, who discusses the transformative impact of minimally invasive surgery and sentinel lymph node mapping. The conversation highlights the importance of specialized gynecologic oncologists in improving surgical and survival outcomes. The series will continue to explore cutting-edge topics, providing oncologists with the latest insights to enhance patient care.

OncLive has launched a new podcast series, From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD.

New OncLive Podcast Series Launches With Focus on Gynecologic Oncology

HR+ Breast Cancer | 
Image Credit: © Rasi 
- stock.adobe.com

Data from the phase 3 VIKTORIA-1 trial (NCT05501886) demonstrated that treatment with the combination of the PI3K/AKT/mTOR (PAM) inhibitor gedatolisib and fulvestrant (Faslodex), with or without palbociclib (Ibrance), generated a clinically meaningful and statistically significant improvement in progression-free survival (PFS) in patients with hormone receptor (HR)–positive, HER2-negative, 

 wild-type advanced breast cancer following progression on or after treatment with a CDK4/6 inhibitor and an aromatase inhibitor.

The benefits of PAM inhibition were seen in results from VIKTORIA-1 presented at the 

 In addition to PFS, gedatolisib also showed gains in median duration of response (DOR) and incremental objective response rates (ORRs) compared with fulvestrant alone.

“VIKTORIA-1 is the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival with PAM inhibition in patients with 

 wild-type disease, all of whom received prior CDK4/6 inhibitor,” Sara A. Hurvitz, MD, FACP, senior vice president and director, Clinical Research Division, Fred Hutchinson Cancer Center, said during a presentation of the data.

How Significantly Did Gedatolisib Improve PFS and Other Efficacy End Points?

Compared with fulvestrant alone (arm C), both the triplet of gedatolisib, fulvestrant, and palbociclib (arm A) and the doublet regimen of gedatolisib plus fulvestrant (arm B) induced superior PFS. The triplet reduced the risk of disease progression by 76% compared with fulvestrant alone (median PFS, 9.3 months [95% CI, 7.2-16.6] vs 2.0 months [95% CI, 1.8-2.3], respectively; hazard ratio, 0.24; 95% CI, 0.17-0.35; 

 < .0001). The doublet reduced the risk of progression by 67% vs fulvestrant alone (7.4 months [95% CI, 5.5-9.9] vs 2.0 months [95% CI, 1.8-2.3], respectively; hazard ratio, 0.33; 95% CI, 0.24-0.48; 

Superior median PFS was consistent across subgroup analyses for both the triple and doublet regimens. Most noteworthy, according to Hurvitz, was that patients who received prior palbociclib benefited from the triplet regimen. “This is the first time that data in the randomized setting suggested benefit to palbociclib rechallenge,” she said.

When comparing median PFS benefit between arms A and B, the triplet regimen demonstrated higher clinical benefit in almost all subgroups, including those who were pre- and perimenopausal and endocrine therapy–resistant, with visceral metastases, and for those who had previously received treatment with palbociclib.

At a data cutoff of May 30, 2025, data for overall survival (OS) were immature, with only 48% of the protocol-specified events, Hurvitz noted. Compared with 18.5 months (95% CI, 15.8-not estimable [NE]) in the monotherapy arm, the triplet and doublet regimens, respectively, demonstrated a median OS of 23.7 months (95% CI, 21.4-NE; hazard ratio, 0.69; 95% CI, 0.43-1.12; 

 = .1328) and not reached (NR; 95% CI, NR-NR; hazard ratio, 0.74; 95% CI, 0.46-1.19; 

Sixty-three patients in the fulvestrant arm crossed over to the triplet (n = 52; 48.1%) or doublet (n = 11; 10.2%) regimens. This could impact overall survival, Hurvitz said, adding that a sensitivity analysis performed at the time of crossover showed a greater separation of the OS curves in favor of the triplet (hazard ratio, 0.60; 95% CI, 0.35-1.04; 

 = .0698) and doublet (hazard ratio, 0.56; 95% CI, 0.33-0.97; 

“The study is continuing to follow patients for overall survival, with final analysis anticipated about 48 months after the first patient was randomized, or early 2027,” she added.

Tumor response was also superior in both the triple and doublet regimens, compared with fulvestrant alone. In the triplet arm, the ORR was 31.5%. There was 1 complete response (CR), 38 partial responses (PRs), 67 patients with stable disease (SD), and 17 patients with progressive disease (PD). Further, the clinical benefit rate (CBR; defined as CR, PR, and SD > 24 weeks) among this arm was 50%, with a disease control rate (DCR; defined as CR, PR, and SD) of 85.5%. The DOR was a median of 17.5 months (95% CI, 8.8-NE).

In the doublet arm, the ORR was 28.3%, with no CRs, 32 PRs, 55 with SD, and 26 with PD. CBR and DCR were 48.7% and 77.0%, respectively, with a median DOR of 12.0 months (95% CI, 8.1-NE).

Lastly, in the monotherapy arm, the ORR was 1.0%, with no CRs, 1 PR, 40 with SD, and 62 with PD. The CBR and DCR were 11.4% and 39.0%, respectively, with the median DOR not reached.

What Is the Safety Profile of Gedatolisib?

Treatment with gedatolisib was generally well tolerated in both arms with no new safety signals, according to Hurvitz.

In total, 3 patients in the triplet arm and 4 in the doublet arm discontinued treatment due to a treatment-related adverse effect (TRAE). Two deaths occurred in the triplet therapy arm.

TRAEs of interest with the triplet and doublet regimens were stomatitis (any grade, 69.2% and 56.9%, respectively), rash (any grade, 27.7% and 32.3%), diarrhea (any grade, 16.9% and 12.3%), and hyperglycemia (any grade, 9.2% and 11.5%).

Why Is PAM Pathway Investigation Significant?

The PAM pathway drives breast cancer growth and contributes to endocrine and CDK4/6 inhibitor resistance; however, as most available therapies are indicated only for patients with 

-pathway activation, an unmet need remains for those with wild-type disease.

“Therapeutic attempts to completely block the PAM pathway have been limited by toxicity,” Hurvitz explained. “Most available therapies target a single component of the pathway and have modest efficacy limited to biomarker-selected patient populations.”

Following preliminary clinical activity of gedatolisib in combination with palbociclib and fulvestrant as a therapy in the second line and beyond among patients with HR-positive, HER2-negative advanced breast cancer, the investigators aimed to evaluate the highly potent multitarget PAM inhibitor in this patient population following progression on a CDK4/6 inhibitor and aromatase inhibitor.

What Is the Design of the VIKTORIA-1 Trial?

In the open-label, randomized phase 3 trial, 392 patients were randomly assigned 1:1:1 to receive one of the following regimens:

Triplet (arm A; n = 131): 180 mg intravenous gedatolisib once weekly for 3 weeks on and 1 week off, 125 mg palbociclib daily for 21 days and 7 days off, and 500 mg fulvestrant on days 1 and 15 in cycle 1, followed by every 4 weeks;

Doublet (arm B; n = 130): The same gedatolisib and fulvestrant dosing regimens as arm A; or

Monotherapy/control (arm C; n = 131): the same fulvestrant dosing regimen as used in the investigational arms.

Patients treated with fulvestrant monotherapy were allotted the option to cross over to arms A or B at progression.

Pre- and postmenopausal patients were eligible for the trial if they had progression on or after treatment with a CDK4/6 inhibitor and aromatase inhibitor, 2 or more lines of prior endocrine therapy for advanced breast cancer, measurable disease via RECIST v1.1, and a screening result for 

 status. Patients were ineligible if they had type 2 diabetes mellitus with a hemoglobin A

 of greater than 6.4% or type 1 diabetes mellitus; prior therapy with an mTOR, PI3K, or AKT inhibitor; or chemotherapy treatment for their advanced breast cancer.

Patients were stratified by lung/liver metastases, time to progression on their immediate prior therapy, and region.

The co–primary end points were PFS in arm A compared with arm C and PFS in arm B vs arm C. Secondary end points included OS, ORR, safety, and quality of life.

Demographics and baseline characteristics were generally well balanced across treatment arms.

What Is the Future Direction of Gedatolisib?

“We are very excited that treatment with gedatolisib combined with fulvestrant with or without palbociclib was well tolerated by the VIKTORIA-1 patients and that only a few patients discontinued treatment due to an adverse event,” said Igor Gorbatchevsky, MD, chief medical officer of Celcuity, in a press release.

“This safety profile combined with the 7.3- and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens, offer potentially paradigm-shifting results for patients with HR-positive, HER2-negative, 

 wild-type advanced breast cancer,” he added.

According to the release, a rolling new drug application (NDA) has been submitted in tandem with the FDA’s Real-Time Oncology Review Program based on data from the 

 wild-type cohort of the phase 3 VIKTORIA-1 trial. The NDA is expected to be completed before the end of 2025, and topline data from the trial is expected in the first half of 2026. The phase 3 VIKTORIA-2 trial (NCT06757634), designed to evaluate gedatolisib in the frontline setting, is ongoing.

Disclosures: Hurvitz serves in a consulting or advisory role for ALX Oncology, Bayer HealthCare Pharmaceuticals, BeOne, Blueprint Medicines, BriaCell, BridgeBio Oncology Therapeutics, Bristol Myers Squibb, Daiichi Sankyo Inc, EMBioSys, Genentech, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Luminate, Mersana Therapeutics Inc, Novartis, and Prelude Therapeutics. She receives contracted research support as a principal investigator from Arvinas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Celcuity, Daiichi Sankyo Inc, Dantari, Eli Lilly and Company, F. Hoffmann-La Roche Ltd, G1 Therapeutics Inc, Genentech, Gilead Sciences Inc, GSK, Greenwich LifeSciences Inc, Jazz Pharmaceuticals Inc, MacroGenics Inc, Menarini Group, Novartis, Orum Therapeutics, Pfizer Inc, Radius Health Inc, Sanofi, Seagen Inc, Stemline Therapeutics Inc, and Zymeworks Inc. Hurvitz also serves on data and safety monitoring boards/committees for Atossa Therapeutics, InClin, Quantum Leap Healthcare Collaborative, and Roche. Hurvitz receives royalties from Elsevier, McGraw-Hill, Sage, Springer, Wiley, and Wolters Kluwer. Hurvitz serves as an integration panel member for the US Department of Defense Congressionally Directed Medical Research Program, Breast Cancer Research Program. Hurvitz also holds stock in ROMTech (spouse).

Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with and without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.

Detailed results from PIK3CA wild-type cohort of phase 3 VIKTORIA-1 trial presented at 2025 ESMO Congress demonstrate potential for gedatolisib regimens to be practice changing for patients with HR+/HER2- advanced breast cancer. News release. Celcuity. October 18, 2025. Accessed October 18, 2025. https://www.globenewswire.com/news-release/2025/10/18/3168946/0/en/Detailed-Results-from-PIK3CA-Wild-Type-Cohort-of-Phase-3-VIKTORIA-1-Trial-Presented-at-2025-ESMO-Congress-Demonstrate-Potential-for-Gedatolisib-Regimens-to-be-Practice-Changing-for.html

The phase 3 VIKTORIA-1 trial evaluated the efficacy of gedatolisib combined with fulvestrant, with or without palbociclib, in HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer patients. Results showed significant improvements in progression-free survival (PFS) compared to fulvestrant alone, with the triplet regimen reducing disease progression risk by 76%. The trial also demonstrated superior objective response rates and duration of response. Gedatolisib was well-tolerated, with manageable adverse effects. A rolling NDA has been submitted, and further trials are ongoing to explore gedatolisib's potential in frontline settings.

Gedatolisib plus fulvestrant, with or without palbociclib, improved PFS in pretreated, HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer.

Gedatolisib Plus Fulvestrant ± Palbociclib Drives PFS Improvement in PIK3CA Wild-Type, HR+/HER2– Advanced Breast Cancer

Silas is the senior vice president, content, at MJH Life Sciences. He began his career at MJH in 2011 as a Web Editor on OncLive. From this role, he moved into managing the social media across the organization and then into broader roles across the content department, first taking on management of HCPLive.

Throughout his tenure at MJH, Silas has been accountable for several organic launches of highly successful brands, including Targeted Oncology and NeurologyLive, and for quickly transforming acquisitions into high-functioning business units. Follow him on X @

The combination of the oral selective estrogen receptor degrader (SERD) giredestrant combined with everolimus led to a significant reduction in the risk of progression or death compared with standard of care (SOC) endocrine therapy plus everolimus (Afinitor) for patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor, according to primary results from the phase 3 evERA trial (NCT05306340) presented at the 

In the intent-to-treat (ITT) population, the median progression-free survival (PFS) was 8.77 months (95% CI, 6.60-9.59) with giredestrant plus everolimus compared with 5.49 months (95% CI, 4.01-5.59) with SOC (HR, 0.56; 95% CI, 0.44-0.71; 

< .0001). In a subpopulation defined by the presence of the 

 mutation, the giredestrant combination elicited a median PFS of 9.99 months (95% CI, 8.08-12.94) compared with 5.45 months (95% CI, 3.75-5.62) for those treated with SOC (HR, 0.38; 95% CI, 0.27-0.54; 

“The combination of giredestrant and everolimus—an oral SERD and an oral mTOR inhibitor—may represent a new, effective, all-oral treatment option in the post–CDK4/6 inhibitor setting for patients with ER-positive, HER2-negative advanced disease,” lead investigator Erica L. Mayer, MD, MPH, medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Farber Cancer Institute, said during a presentation of the results. “Consistent benefit with this regimen was seen across key subgroups. Overall response and duration of response benefits were observed in all patients. Overall survival is immature yet favorable.”

The evERA study enrolled 373 patients and randomly assigned them to giredestrant plus everolimus (n = 183) or SOC endocrine therapy plus everolimus (n = 190). Giredestrant was administered at 30 mg and everolimus was given at 10 mg in both arms. Patients were stratified based on their 

 status, site of disease, and prior treatment with fulvestrant. Of note, 

 mutations were present in 102 of those in the giredestrant arm and in 105 in the SOC group at baseline. The most common SOC therapy was exemestane (n = 141), followed by fulvestrant (n = 39) and tamoxifen (n = 6).

Baseline demographics and characteristics were balanced across the groups, Mayer mentioned. In the giredestrant arm, the median age was 62 years. Visceral disease was present for 68.9% of patients, most commonly in the liver (n = 89). Bone-only metastases were present for 13.1% of patients. Most patients (76.5%) had received at least 1 prior line of therapy for advanced breast cancer, with 21.9% having received 2 and 1.6% having received none. All patients had received a prior CDK4/6 inhibitor. Nearly half of the patients had received prior fulvestrant (47%).

 subgroup and in the full ITT population were the co–primary end points of the study. Secondary end points included overall survival (OS), objective response rate (ORR), and duration of response (DOR).

The PFS Kaplan-Meier curves separated early and continued to widen, Mayer noted. In the 

 group, at 6 months, 66.1% of those in the giredestrant group remained progression-free compared with 38.1% in the control arm. At month 12, the PFS rates were 40.5% and 15.2%, respectively. In the ITT population, the 6-month PFS rate was 57.4% with giredestrant compared with 39.6% for SOC. At 12 months, the PFS rates were 34.1% and 18.1%, respectively.

An exploratory analysis found similar PFS rates regardless of the endocrine therapy used in the SOC arm. In the 

 group, the hazard ratios for giredestrant/everolimus compared with exemestane/everolimus and fulvestrant/everolimus were 0.40 (95% CI, 0.28-0.58) and 0.44 (95% CI, 0.28-0.69), respectively. For those in the ITT group, the HRs were 0.55 (95% CI, 0.43-0.71) and 0.59 (95% CI, 0.40-0.86), respectively.

“Treatment with giredestrant and everolimus has consistent benefit across all key subgroups,” Meyer said. “This includes patients with visceral disease, liver involvement, prior treatment with fulvestrant, and, I would add, in the 

Interim findings were presented for OS, which had reached 59% maturity in the 

 population and 67% maturity in the ITT group. In the 

 group, median OS was not yet reached in the giredestrant group compared with 21.03 months for those treated with SOC (HR, 0.62; 95% CI, 0.38-1.02; 

 = .0566). In the ITT population, median OS was not yet reached in the giredestrant arm compared with 26.87 months in the SOC arm (HR, 0.69; 95% CI, 0.47-1.00; 

An exploratory analysis was conducted, looking at PFS and OS in patients without detected 

 mutations. In this subgroup, the median PFS was 5.72 in the giredestrant group compared with 5.52 in the SOC group (HR, 0.84; 95% CI, 0.59-1.18). The median OS in this group was not reached in either arm (HR, 0.79; 95% CI, 0.44-1.40).

-mutant group, the ORR was 26.6% with giredestrant compared with 13.8% with SOC. In the ITT group, the ORR was 23.8% with giredestrant and 11.7% with SOC. In those without the 

 mutation, the ORR was 20.0% with giredestrant and 8.7% with SOC.

The median DOR was longer in the giredestrant arm. In the 

-mutant population, the median DOR was 14.88 months compared with 7.33 months for SOC. For the ITT group, the DOR was 12.71 months compared with 7.72 months, for giredestrant and SOC, respectively. For those without an 

 mutation detected, the median DOR was 12.68 months with giredestrant compared with 7.72 months with SOC.

“Treatment with giredestrant and everolimus led to a consistent doubling in the response rate, seen in the 

 population [and] the ITT population, as well as those without 

 mutation,” said Mayer. “These were durable responses, as the duration of response was consistently prolonged in all 3 subgroups. Notably, in the 

-mutant population, the duration of response doubled from about 7 months with standard of care and everolimus therapy to almost 15 months of disease control with giredestrant.”

In the investigational arm, the median treatment duration was 7.11 months with giredestrant and 6.03 months for everolimus. Adverse events led to treatment discontinuation for 17% of those in the giredestrant group compared with 11.8% of those in the SOC arm. The median dose intensity was 95.98% for giredestrant and 84.70% for everolimus. In the control group, the median treatment duration was 4.62 months for endocrine therapy and 4.14 months for everolimus. The median dose intensity was 96.65% for the endocrine therapy and 87.86% for everolimus.

The most common all-grade treatment-emergent adverse effects in the giredestrant and SOC arms were stomatitis (47.2% vs 48.9%, respectively), diarrhea (26.9% vs 22.6%), and anemia (23.6% vs 21.0%). Of note, Mayer noted that grade 1/2 bradycardia occurred in 3.8% of those treated with giredestrant compared with 0.5% of those in the SOC group. There were no cases of photopsia seen in the study.

“Assessment of toxicity is influenced by the longer median treatment duration in the giredestrant arm,” said Mayer. “Overall, however, the toxicity experience was fairly balanced between the 2 arms and reflects the known safety profiles of the individual study agents.”

According to Roche, the developer of giredestrant, data from the evERA study would be “shared with health authorities, with the aim of bringing this potential treatment option to people as soon as possible,” according to a statement from the company.

Disclosures: Mayer serves in a consulting or advisory role for AstraZeneca, Aktis, Genentech, Lilly, and Novartis. She received research support in the form of third-party medical writing assistance for the presentation from F. Hoffmann-La Roche.

Mayer E, Tolaney SM, Martin M, et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA16.

Roche’s phase III evERA data showed giredestrant significantly improved progression-free survival in people with ER-positive advanced breast cancer. News release. Roche. October 17, 2025. Accessed October 18, 2025. https://www.roche.com/media/releases/med-cor-2025-10-18

The combination of giredestrant, an oral selective estrogen receptor degrader, with everolimus significantly reduced the risk of progression or death in patients with ER-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor. The phase 3 evERA trial demonstrated improved progression-free survival (PFS) and objective response rates (ORR) compared to standard endocrine therapy plus everolimus. The regimen showed consistent benefits across key subgroups, including those with ESR1 mutations. Adverse events were manageable, and the treatment's safety profile was consistent with known agents. Data will be shared with health authorities for potential approval.

Giredestrant plus everolimus improved progression-free survival in ER-positive, HER2-negative advanced breast cancer after a prior CDK4/6 inhibitor.

Nicole Canfora Lupo

Articles

New OncLive Podcast Series Launches With Focus on Gynecologic Oncology

Gedatolisib Plus Fulvestrant ± Palbociclib Drives PFS Improvement in PIK3CA Wild-Type, HR+/HER2– Advanced Breast Cancer

Giredestrant/Everolimus Extends PFS for ER+, HER2– Advanced Breast Cancer