Kristie L. Kahl is vice president of content at MJH Life Sciences, overseeing CURE®, CancerNetwork®, the journal ONCOLOGY, Targeted Oncology, and Urology Times®. She has been with the company since November 2017.

She is a graduate of Rider University, where she acquired a Bachelors of Art in journalism, as well as a graduate of Temple University, where she received her Masters of Science in Sports Management.

Follow Kristie on Twitter at @KristieLKahl, or email her at kkahl@mjhlifesciences.com.

Kristie L. Kahl

Among older patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), Epkinly plus R-mini-CHOP appeared to be well tolerated and elicited responses.

Among older patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), treatment with fixed-duration Epkinly (epcoritamab-bysp) plus dose-attenuated Rituxan (rituximab) plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-mini-CHOP) appeared to be well tolerated and elicited responses, clinical trial data have shown.

Data from arm 8 of the phase 1/2 EPCORE NHL-2 trial, which were presented at the 2025 ASH Annual Meeting, showed that at a median follow-up of 33.4 months, the overall response rate (ORR) in all patients (28 patients) was 93%, which was comprised of a complete response (CR) rate of 86% and a partial response (PR) rate of 7%. The median time to response was 1.4 months and the median time to CR was 1.6 months.

At two years, 79% of patients remained in response to treatment with the regimen, and 79% remained in CR. Of the 22 patients who completed therapy, 20 experienced a CR at the end of treatment (91%). At a median follow-up of 22.6 months after the end of treatment, 90% of the 20 patients remained in CR. Moreover, the two-year progression-free (PFS) and overall survival (OS) rates were 76% and 82%, respectively. The median PFS and OS were not reached irrespective of International Prognostic Index score.

Overall Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment. It includes both partial and complete responses.

Progression-Free Survival (PFS): The length of time during and after treatment that the cancer does not grow or get worse.

Overall Survival (OS): How long patients stay alive after diagnosis or the start of treatment, regardless of whether the cancer returns or progresses.

International Prognostic Index (IPI) Score: A tool doctors use—especially for certain lymphomas—to estimate how aggressive the disease may be. It considers factors such as age, stage of cancer, symptoms, and some blood test results to help guide treatment planning.

Minimal Residual Disease (MRD): A very small amount of cancer cells that remain in the body after treatment, even when tests show no obvious signs of disease. Highly sensitive tests can detect MRD and help doctors understand the risk of the cancer returning.

Myocardial Infarction: The medical term for a heart attack. It happens when blood flow to part of the heart is blocked, causing heart muscle damage.

Elevated Lactate Dehydrogenase (LDH): Higher-than-normal levels of an enzyme found in many tissues. When LDH is elevated in blood tests, it can be a sign of cell damage or inflammation and may help doctors understand how active the cancer is.

Neutropenia: A low number of neutrophils, a type of white blood cell that fights infection. Neutropenia can increase the risk of infections and is a common side effect of chemotherapy.

Cytokine Release Syndrome (CRS): An inflammatory reaction that can happen when certain cancer treatments activate the immune system very strongly. Symptoms can include fever, fatigue and low blood pressure. Doctors monitor for CRS closely.

Hypokalemia: A lower-than-normal level of potassium in the blood. Potassium helps muscles and nerves function properly. Low levels can cause weakness, cramps, or irregular heartbeats.

Of the 21 patients evaluable for minimal residual disease (MRD), 20 (95%) were negative at the time of the data cutoff date of Sept. 21, 2025. At the first assessment, which was done on day 1 of cycle 3, 80% (16) of patients achieved MRD negativity. Of the four MRD-positive patients at this assessment, three converted to MRD negativity by the second assessment, which was done on day 1 of cycle 6; two patients experienced subsequent progressive disease. Notably, MRD negativity was observed across all patient subgroups, including bulky disease (89%) and those with an IPI score ranging from 3 to 5 (93%).

“We can conclude that in combination with dose-attenuated chemotherapy, [Epkinly] may have a role in the treatment of patients with historically poor outcomes,” Dr. Chan Cheah, of the Sir Charles Gairdner Hospital and the University of Western Australia, in Nedlands, Australia, said during a presentation of the data.

Although R-mini-CHOP is the standard of care (SOC) for patients with newly diagnosed DLBCL who are not able to receive the full dose, outcomes with the regimen remain suboptimal, Cheah explained. “It’s clear that better options for these patients are required,” he added. Previously, the CD3xCD20 bispecific antibody Epkinly was found to be efficacious when administered as a monotherapy or paired with SOC in those with newly diagnosed DLBCL.

For example, findings from the phase 2 EPCORE DLBCL-3 trial indicated that single-agent Epkinly induced durable responses in patients with newly diagnosed large B-cell lymphoma and comorbidities. Other findings from EPCORE NHL-2 showed that the combination of Epkinly and R-mini-CHOP elicited an ORR of 89% and a CR rate of 82% in elderly patients with newly diagnosed DLBCL who could not receive the full dose of R-CHOP. At the meeting, Cheah shared follow-up data from EPCORE NHL-2.

The open-label, phase 1b/2 trial enrolled patients with newly diagnosed DLBCL, which could have been DLBCL not otherwise specified, T-cell or histocyte-rich DLBCL, high-grade B-cell lymphoma, or grade 3B follicular lymphoma. Patients had an ECOG performance status ranging from 0 to 2 and could not be eligible to receive full-dose R-CHOP because they were 75 years of age or older or 65 years of age or older with a comorbidity.

Twenty-eight patients received a fixed duration of subcutaneous Epkinly at a dose of 48 mg once weekly for cycles 1 and 2 and every three weeks for cycles 3 to 6 and intravenous R-mini-CHOP, which comprised 375 mg/m

 of vincristine — all given every three weeks — and 100 mg/day of prednisone, given on days 1 to 5 of each cycle from cycles 1 to 6. Epkinly was then given at 48 mg every four weeks for cycles 7 to 8.

In terms of baseline characteristics, the median patient age was 81 years. Patients were not eligible to receive a full dose of anthracycline because of age older than 75 years (96%), hypertension requiring treatment (54%), diabetes mellitus (11%) or history of myocardial infarction (4%). Moreover, 43% of patients had an IPI score of 4 to 5 at screening, 39% had a bulky tumor of 7 cm or larger, and the majority had elevated lactate dehydrogenase (64%).

What was the safety profile of Epkinly in this population?

Cheah noted that most side effects were mild to moderate in severity, and no new safety concerns associated with the addition of Epkinly to R-mini-CHOP presented with longer follow-up. The most frequent grade 3 (severe) or higher treatment-emergent side effects were neutropenia (43%), serious infections (32%) and anemia 14%). Most grade 3 or higher serious infections were reported within the first six cycles of treatment, when R-mini-CHOP was being coadministered.

The most common treatment-emergent side effect was cytokine release syndrome (CRS), which occurred in 61% of patients; this effect was grade 1 (mild) for 32% of patients and grade 2 (moderate) for 29% of patients. Time to first onset of CRS occurred at a median of 16 days. Patients were treated with either Actemra (tocilizumab; 29%) or corticosteroids (14%), leading to CRS resolution across all patients affected. The median time to resolution was two days. CRS led to treatment discontinuation in one patient. Cheah noted that almost all (90%) CRS events occurred in cycle 1 of treatment.

Additional common treatment-emergent side effects occurring in 20% or more patients were neutropenia, serious infections, anemia, constipation, fatigue, hypokalemia and fall. No patients experienced immune effector cell–associated neurotoxicity syndrome (ICANS) or tumor lysis syndrome (TLS).

TEAEs led to discontinuation of Epkinly in three patients (11%), including one fatal event, and discontinuation of R-mini-CHOP in six patients (21%).

What is the significance of the updated EPCORE NHL-2 data?

“Despite an older population of newly diagnosed diffuse large B-cell lymphoma, the outcomes observed in arm 8 of the EPCORE NHL-2 evaluating fixed-duration Epkinly plus R-mini-CHOP are encouraging,” Cheah stated in a news release issued by Genmab. “These results, along with those from other arms of the trial, support the potential for combinations of Epkinly with standard of care treatment across a range of disease settings and patient populations.”

“Epcoritamab + R-mini-CHOP results in 2-year remissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial” by Dr. Chan Cheah et al., presented at: 2025 ASH Annual Meeting; Dec. 6 to 9, 2025; Orlando, Florida. Abstract 64.

“Fixed-duration epcoritamab monotherapy induces high response and MRD-negativity rates in elderly patients with newly diagnosed large B-cell lymphoma (LBCL) and comorbidities: Results from EPCORE DLBCL-3” by Dr. Umberto Vitolo et al., presented at: 2025 ASH Annual Meeting; December 6 to 9, 2025; Orlando, Florida. Abstract 63.

“Fixed-duration epcoritamab + R-mini-CHOP in patients with previously untreated diffuse large B-cell lymphoma ineligible for full-dose R-CHOP: Updated results from arm 8 of the Epcore NHL-2 trial,” by Dr. Chan Cheah et al. 

. 2024;144(suppl 1):3106. doi: 10.1182/blood-2024-199652

“Genmab announces data from multiple clinical trials showing treatment with fixed-duration epcoritamab led to remissions in first-line diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL),” news release; https://ir.genmab.com/news-releases/news-release-details/genmab-announces-data-multiple-clinical-trials-showing-treatment

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Articles

A study on older patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) demonstrated that a regimen combining Epkinly (epcoritamab-bysp) with dose-attenuated R-mini-CHOP was well tolerated and effective. The trial showed a high overall response rate (ORR) of 93%, with a complete response (CR) rate of 86%. At two years, 79% of patients remained in CR. The treatment was associated with manageable side effects, primarily cytokine release syndrome. These findings suggest potential benefits of Epkinly in combination with standard care for this patient population.

Older Patients With DLBCL May Benefit From First-Line Epkinly Plus R-mini-CHOP

Transitioning treatment with Niktimvo to a dose of 0.6 mg/kg every four weeks appeared feasible for chronic graft-versus-host disease.

Among patients experiencing chronic graft-versus-host disease (cGVHD), the transition of treatment with Niktimvo (axatilimab) to a dose of 0.6 milligrams per kilogram (mg/kg) every four weeks appeared feasible among those treated with a dose of 0.3 mg/kg every two weeks, according to data from the pivotal phase 2 AGAVE-201 trial.

“Overall, these findings support the safety and feasibility of [Niktimvo] at a dose of 0.6 mg/kg monthly,” Dr. Nosha Farhadfar of Methodist Physicians Texas Transplant Specialists - Adult Blood Marrow Transplant, San Antonio in Texas, said during a presentation of the data at the 2025 ASH Annual Meeting. “Future analyses are planned to further evaluate the efficacy and safety at this dosing. Also, I think we need real-world evidence, which is essential to complement this finding and provide a broader support for the therapeutic approach.”

Graft-Versus-Host Disease (GVHD): A possible complication after an allogeneic stem cell transplant. It happens when the donor’s immune cells see the patient’s body as foreign and begin to attack it. Symptoms can range from skin rashes to stomach or liver problems.

Creatine Phosphokinase (CPK) Increase: A rise in the level of an enzyme found in muscles. Higher levels in blood tests can mean the muscles are irritated, inflamed, or injured. 

Oropharyngeal Pain: Pain in the back of the mouth or throat. It can happen due to infections, irritation from treatments, or mouth sores.

Pruritus: A medical word for itching. It can be mild or intense and may be caused by treatment, dry skin, or certain medical conditions.

Pyrexia: The medical term for fever — when body temperature is higher than normal. Fever can be a sign of infection or inflammation and should be reported to a healthcare team.

In the AGAVE-201 trial, patients who met pre-specified criteria could change their dosing schedule from 0.3 mg/kg every two weeks to 0.6 mg/kg every four weeks, without dose capping. Investigators evaluated the safety and feasibility of transitioning from the approved dose using long-term data from the trial.

Among the 19 patients who transitioned to the 0.6-mg/kg dose, the median age was 50 years, with the majority being male (63.2%). Median time from diagnosis to randomization was 4.39 months and the median number of organs involved was three. The majority of patients reported with severe disease (73.7%), and had previously received an FDA-approved agent (89.5%).

“The subgroup that transitioned to monthly dosing was generally comparable to the overall [population who received the 0.3 mg/kg dose every two weeks,]” Farhadfar said.

Treatment with a dose of 0.6 mg/kg every 4 weeks led to an overall response rate of 94.7%, including partial and complete response rates of 89.5% and 5.3%, respectively.

“One patient with stable disease was transitioned to multi-dosing at the investigator’s discretion,” Farhadfar added.

After switching doses, patients were on treatment for a median of 20.9 months. At data cutoff, 16 patients (84.2%) maintained the 0.6 mg/kg dose. Of the three who did not, two patients switched back to the FDA-approved dose at 4.6 and 18.6 months following the switch, respectively, while one patient switched back due to an side effect at 3.4 months. In the overall population, the treatment duration was 7.4 months.

Farhadfar noted that the incidence of grade 3 (severe)or higher side effects was higher with the monthly dose compared with the FDA-approved dose (52.6% versus 36.8%, respectively), which was to be expected given the longer treatment duration seen.

“However, when you look at the incidence of treatment-related adverse event, this is similar before and after the monthly dosing, suggesting that the increase in adverse event may be more reflective of longer treatment exposure rather than the direct effect of a new dosing schedule.”

After the switch, there was also a higher incidence of serious side effects (42.1% versus 5.3%, respectively); however, less patients had dose interruptions (21.1% versus 36.8%). Investigators saw a slight increase in the amount of dose reductions (three versus none, respectively) and discontinuations (three versus none).

The most common side effects included fatigue (26.3%), upper respiratory tract infection (26.3%), headache (21.1%), abdominal pain (15.8%), cough (15.8%), creatine phosphokinase increase (15.8%), diarrhea (15.8%), falls (15.8%), oropharyngeal pain (15.8%), pruritis (15.8%) and pyrexia (15.8%).

In August 2024, the FDA approved Niktimvo 0.3 kg/mg every two weeks for the treatment of cGVHD in patients who previously received two or more lines of therapy, based on results from the AGAVE-201 trial. Farhadfar emphasized that the 0.6-mg/kg dose is an investigational schedule change.

“So we need to interpret the results [cautiously], as the available efficacy data for the monthly dosing are limited and the sample size is very small,” she added. “My personal preference is to keep the patient at the every-two-weeks dosing, and consider transitioning to monthly dosing only in a situation where the patients are unable, unwilling or there are some challenges that make this every-two-weeks dosing impractical.”

“Safety and feasibility of 0.6 mg/kg every 4 weeks dosing of axatilimab in patients treated in the AGAVE-201 study,” by Dr. Nosha Farhadfar et al., 

The AGAVE-201 trial evaluated the feasibility of transitioning chronic graft-versus-host disease (cGVHD) patients from a 0.3 mg/kg biweekly dose of Niktimvo (axatilimab) to a 0.6 mg/kg monthly dose. Results showed a high overall response rate of 94.7%, with increased severe side effects due to longer treatment duration. Despite the promising response, the investigational dose requires cautious interpretation due to limited efficacy data and small sample size. The FDA-approved dose remains 0.3 mg/kg biweekly, with monthly dosing considered only when biweekly dosing is impractical.

Higher Niktimvo Dosing Feasible in Chronic Graft-Versus-Host Disease

Trodelvy plus Keytruda may maintain quality of life and slow physical decline in metastatic triple-negative breast cancer.

Among patients with previously untreated, PD-L1-positive metastatic triple-negative breast cancer (mTNBC), treatment with Trodelvy (sacituzumab govitecan) plus Keytruda (pembrolizumab) has been shown to possibly lead to maintained quality of life (QOL).

Patient reported outcomes (PROs) from the phase 3 ASCENT-04/KEYNOTE-D19 study were presented at the 2025 ESMO Congress, showing the combination may potentially provide a delay in the onset of physical decline.

“[Trodelvy] plus [Keytruda] maintained overall QOL,” Dr. Evandro de Azambuja, head of the Medical Support Team at the Jules Bordet Institute, Brussels, Belgium, said during a presentation of the data. “Patients reported reduced symptom burden and improved functioning in multiple domains. These data complement the clinically meaningful improvement in progression-free survival and support this treatment regimen as a potential new standard of care for patients with PD-L1–positive mTNBC.”

Progression-free survival (PFS): This is the length of time a person lives while taking a cancer treatment during which the cancer does not get worse or grow.

Duration of response (DOR): This is the time span that the cancer remains significantly shrunk or completely gone after a treatment has successfully worked.

Neutropenia: This is a condition where you have an abnormally low number of neutrophils, which are a type of white blood cell important for fighting infection.

Did the combination of Trodelvy plus Keytruda improve symptom burden?

Time to deterioration in physical functioning was comparable between the Trodelvy plus Keytruda and chemotherapy plus Keytruda groups (median, three months versus 3.5 months).

However, the sensitivity analysis showed prolonged time to first deterioration with the Trodelvy regimen compared with chemotherapy (median, 9.3 months versus 6.9 months). Time to confirmed deterioration through the sensitivity analysis also showed a prolonged duration of 8.8 months with Trodelvy plus Keytruda versus 5.7 months with Keytruda plus chemotherapy.

“Both sensitivity analyses consistently showed that [Trodelvy] plus [Keytruda] has a numerically longer time to deterioration and may delay the onset of decline in physical functioning,” de Azambuja said. “If you look into different domains, quality of life was maintained across different domains.”

According to time to deterioration, emotional functioning (median, 9.3 months versus 4.9) and pain (median, 4.3 versus 3.2) were favored with Trodelvy plus Keytruda compared with Keytruda plus chemotherapy.

“There was worsening of symptoms such as nausea/vomiting and diarrhea, which are consistent with the safety profile of the [Trodelvy] plus [Keytruda] group in the study and can be managed by following established guidelines,” de Azambuja said.

Lastly, from baseline to EORTC QLQ-C30 scores, the Trodelvy regimen was more favorable compared with the chemotherapy regimen for physical (least squares mean change, 2.45), role (3.34), and emotional (4.07) functioning, as well as pain (-5.39) and insomnia (-4.59).

According to de Azambuja, approximately 50% of patients with mTNBC who receive first-line treatment do not receive second-line therapy, which includes a substantial deterioration in QOL with each line of therapy. He added that frontline therapy may be an important opportunity to control disease without worsening QOL.

“Patient-reported outcome will provide insight from impact on treatments including symptom burden and functional status,” de Azambuja said.

The investigators evaluated QOL as a secondary end point of the trial, including time to deterioration in physical functioning and time to deterioration in the role of functioning, GHS/QOL, pain and fatigue.

Patient-reported outcome assessments occurred at baseline, day 1 of all cycles and the end of treatment. Questionnaires were completed in about 70% of treatment arms, de Azambuja noted.

Baseline EORTC QLQ-C30 domain scores were consistent between treatment groups and with general population scores for most domains.

The randomized, open-label, phase 3 trial evaluated the efficacy of Trodelvy in combination with Keytruda versus Keytruda plus physician’s choice of chemotherapy in patients with previously untreated, locally advanced, inoperable or metastatic TNBC whose tumors expressed PD-L1 with a CPS of 10 or greater. Four hundred and forty-three patients were randomized to receive either Trodelvy plus Keytruda (221 patients) or Keytruda plus chemotherapy (222 patients).

The Trodelvy regimen reduced the risk for disease progression by 35% after a median follow-up of 14 months. Further, median duration of response was 16.5 months for Trodelvy plus Keytruda compared with 9.2 months with Keytruda plus chemotherapy.

Of note, the most frequent grade 3 (severe) or higher treatment-emergent side effects with the Trodelvy regimen were neutropenia (43%) and diarrhea (10%) and with the chemotherapy regimen were neutropenia (45%), anemia (16%) and thrombocytopenia (14%).

“The primary analysis of ASCENT-04 showed a statistically significant and clinically important improvement in median progression-free survival with [Trodelvy] plus [Keytruda] as first-line treatment for untreated PD-L1–positive metastatic triple-negative breast cancer,” de Azambuja said.

“Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in patients (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) in the phase III ASCENT-04/KEYNOTE-D19 study,” by Dr. Evandro de Azambuja et al., presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA22.

“Sacituzumab Govitecan Plus Pembrolizumab Improves PFS in PD-L1–Positive mTNBC,” OncLive, April 21, 2025. Accessed Oct. 20, 2025. https://www.onclive.com/view/sacituzumab-govitecan-plus-pembrolizumab-improves-pfs-in-pd-l1-positive-mtnbc.

“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,” by Dr. Sara M. Tolaney, et al., 

. 2025;43(suppl 17). doi:10.1200/JCO.2025.43.17_suppl.LBA109

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The combination of Trodelvy (sacituzumab govitecan) and Keytruda (pembrolizumab) in treating PD-L1-positive metastatic triple-negative breast cancer (mTNBC) has shown potential in maintaining quality of life (QOL) and delaying physical decline. The phase 3 ASCENT-04/KEYNOTE-D19 study revealed that this regimen may reduce symptom burden and improve functioning across multiple domains, with a significant improvement in progression-free survival. Despite some manageable side effects, the combination therapy demonstrated a longer duration of response compared to Keytruda plus chemotherapy, suggesting a potential new standard of care.

Trodelvy Plus Keytruda Upholds Quality of Life in TNBC

Trodelvy reduced risk of disease progression or death versus chemotherapy in patients with previously untreated metastatic triple-negative breast cancer.

Treatment with Trodelvy (Sacituzumab govitecan) reduced the risk for disease progression or death by 38% versus chemotherapy among patients with previously untreated, locally advanced, unresectable, or metastatic triple-negative breast cancer (TNBC) not eligible for PD-1 or PD-L1 inhibitors, according to data from the phase 3 ASCENT-03 trial presented at the 

In addition to improvements in progression-free survival (PFS), Trodelvy achieved a superior duration of response (DOR) with no new safety signals.

“This data may support a potential new standard and a good option for patients with metastatic TNBC who cannot receive immune checkpoint inhibitors,” said Dr. Javier C. Cortés, head of the International Breast Cancer Centre in Barcelona, Spain.

Among patients treated with Trodelvy, median PFS was 9.7 months versus 6.9 months with chemotherapy. PFS rates were higher with Trodelvy compared with chemotherapy at 6 months (65% versus 53%) and 12 months (41% versus 24%). Investigator-assessed PFS was 9.6 months with Trodelvy versus 6.8 months with chemotherapy. Six- and 12-month PFS rates were 65% and 52% with Trodelvy versus 38% and 22% with chemotherapy.

Progression-Free Survival (PFS): The length of time during and after treatment that a patient’s cancer does not get worse.

Objective Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.

ECOG Performance Status: A scale from 0 to 5 that doctors use to describe how well a patient can carry out daily activities, with 0 being fully active and higher numbers indicating more limitation.

Overall Survival (OS): The length of time from the start of treatment that patients are still alive.

Duration of Response (DOR): How long a patient’s cancer stays shrunk or disappears after responding to treatment.

Intravenous (IV): A way of giving medicine directly into a vein using a needle or tube.


PFS benefit was observed across all subgroups, including by age, ECOG performance status, geographic region, disease state, PD-L1 status, and prior chemotherapy. Objective response rate (ORR) was 48% with Trodelvy versus 46% with chemotherapy. Complete response occurred in 20 patients (7%) versus 15 patients (5%), partial response in 115 (41%) versus 112 (40%), stable disease in 113 (41%) versus 101 (36%), and progressive disease in 14 (5%) versus 36 (13%).

“Objective response rates were similar; however, duration of response was substantially longer with Trodelvy,” Cortés noted. Median DOR was 12.2 months versus 7.2 months with chemotherapy. Time to response was 1.6 months in both groups.

Overall survival (OS) data were not mature at presentation. Among 179 patients who initiated subsequent treatment after chemotherapy, 147 (82%) received Trodelvy. Median OS was 21.5 months versus 20.2 months. Median PFS2 was 18.2 months versus 14.0 months.

Side Effects of Trodelvy During the ASCENT-03 Trial

Median treatment duration with Trodelvy was 8.3 months. Treatment-emergent side effects occurred in 99% versus 97% of patients, with grade 3 or higher side effects in 66% versus 62% and treatment-related events in 61% versus 53%.

There were 71 serious side effects in the Trodelvy arm, 46 treatment related. Side effects led to treatment discontinuation in 10 patients, dose interruptions in 181, and dose reductions in 101. Seven side effects led to death, mostly infections, including five secondary to neutropenia. None of the five patients at risk for febrile neutropenia received prophylaxis with G-CSF.

Most common grade 3 or higher side effects included neutropenia (43%), diarrhea (9%), and leukopenia (7%). Side effects leading to discontinuation occurred in 4% versus 12%.

“Chemotherapy has been the mainstay for metastatic TNBC, and absolute improvements in median OS have been modest,” said Dr. Ana C. Garrido-Castro, Dana-Farber Cancer Institute and Harvard Medical School.

“Approximately 25% to 30% of patients with metastatic TNBC do not survive 6 months from diagnosis, roughly the median PFS of first-line chemotherapy. A new drug that significantly improves PFS with acceptable toxicity should change the first-line standard of care.”

Most patients with previously untreated metastatic TNBC are not candidates for PD-1 or PD-L1 inhibitors. About half do not receive a second-line therapy. “The majority will experience progressive disease and need subsequent therapies. Improved options in earlier lines are urgently needed,” Cortés added.

Trodelvy is approved for metastatic TNBC in the second line and beyond and for pre-treated HR-positive/HER2-negative metastatic breast cancer globally.

In ASCENT-03, patients with previously untreated, locally advanced, unresectable, or metastatic TNBC not eligible for immune checkpoint therapy were randomized 1:1 to receive intravenous (IV) Trodelvy on days 1 and 8 of 21-day cycles (279 patients) or chemotherapy (279 patients).

Treatment continued until progression or unacceptable toxicity. Eligible patients could cross over to second-line Trodelvy after progression. Patients were eligible if not candidates for PD-1 or PD-L1 inhibitors and were 6 months or less since curative treatment. Previously treated stable central nervous system metastases were allowed. PFS by served as the primary end point. Secondary end points included OS, ORR, DOR, time to response, safety, and quality of life.

Median age was 56 versus 54. Most patients were White (64% each), ECOG 0 (66% vs 67%), PD-L1 negative (99% each), had lung metastases (59% vs 61%), received prior neoadjuvant therapy (66% vs 68%), and 48% had recurrence ≥12 months after curative treatment.

"Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)." by Dr. Javier C. Cortés, et al. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin Germany. Abstract LBA20.

"Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer," Dr. Javier C. Cortés. 

For more news on cancer updates, research and education,

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Kristie L. Kahl

Older Patients With DLBCL May Benefit From First-Line Epkinly Plus R-mini-CHOP

Higher Niktimvo Dosing Feasible in Chronic Graft-Versus-Host Disease

Trodelvy Plus Keytruda Upholds Quality of Life in TNBC

Trodelvy in Metastatic Triple-Negative Breast Cancer Supported by Phase 3 Trial

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