Ariana Pelosci

Giredestrant generated improved outcomes over standard endocrine therapy in patients with ER+/HER2–, medium- and high-risk early breast cancer.

Among patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, medium- and high-risk early breast cancer, giredestrant (GDC-9545) improved invasive disease-free survival (IDFS) versus standard-of-care (SOC) endocrine therapy, according to findings from the phase 3 lidERA breast cancer trial presented at the 2025 San Antonio Breast Cancer Symposium (SABCS).

Efficacy data from the trial revealed that in patients treated with giredestrant or SOC endocrine therapy, a significant and clinically meaningful improvement in IDFS was observed with the investigational therapy with a 30% reduction in the risk of invasive disease recurrence or death after a median follow-up of 32.36 months. Additionally the respective 12 month 24 month and 36 month IDFS rates in the giredestrant arm were 97.7% 94.6% and 92.4%. In the SOC arm the respective rates were 96.9% 92.3% and 89.6%.

An exploratory analysis examining IDFS by SOC endocrine therapy regimens revealed that aromatase inhibitors displayed more favorable efficacy versus tamoxifen.

A subgroup analysis revealed that the IDFS benefit was consistent across all key prespecified subgroups. Particular benefit was observed among patients 46 to 55 years old patients with American Joint Committee on Cancer stage II disease at surgery patients who did not receive prior chemotherapy and premenopausal patients.

Additionally interim overall survival (OS) data revealed a numerically improved advantage with giredestrant although the data were immature at the time of analysis. The respective 12 month 24 month and 36 month OS rates in the giredestrant and SOC arms were 99.5% versus 99.4% 98.2% versus 97.5% and 97% versus 95.9%.

“Since the approval of aromatase inhibitors in 2000 25 years later the lidERA breast cancer trial is the first trial that has demonstrated benefit with a novel endocrine agent in early breast cancer,” Dr. Aditya L. Bardia, stated in the press briefing. “With a median follow-up of 32.6 months lidERA demonstrated a clinically meaningful and statistically significant improvement with frontline giredestrant over SOC endocrine therapy in estrogen receptor-positive human epidermal growth factor receptor 2-negative early breast cancer.”

Those enrolled on the phase 3 trial had stage 2 to 3 estrogen receptor-positive human epidermal growth factor receptor 2-negative disease had received breast cancer surgery within 12 months of the start of study treatment and received adjuvant or neoadjuvant chemotherapy if indicated. Patients were stratified by medium versus high-risk disease region receipt of previous chemotherapy and menopausal status.

The primary end point of the trial was invasive disease-free survival excluding second primary non-breast cancer. Secondary end points included disease-free survival distant recurrence-free survival IDFS including second primary non-breast invasive cancer overall survival and safety.

In the safety evaluable population of the giredestrant and endocrine therapy arms the most common treatment-emergent side effects included arthralgia 46.5% versus 45.3% hot flush 27.1% versus 28.5% and headache 15.2% versus 13.1%. Arthralgias and hot flushes resulting in treatment discontinuations in the respective arms occurred in 1.6% versus 3.7% and less than 0.1% versus 0.8% of patients. Of note no patients in either arm experienced grade 3 or 4 bradycardia and less than 0.1% versus 0.3% of each arm experienced grade 3 or 4 venous thromboembolic events.

“The safety profile was favorable and consistent with the known profile. The discontinuation rate was lower with giredestrant compared with standard-of-care endocrine therapy,” Bardia concluded.

“Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: results from the global Phase III lidERA Breast Cancer trial,” by Dr. Aditya L. Bardia, et al. Presented at: 2025 San Antonio Breast Cancer Symposium; Dec. 9-12, 2025; San Antonio, TX. Abstract GS1-10.

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Giredestrant, an investigational therapy, demonstrated improved invasive disease-free survival (IDFS) compared to standard-of-care (SOC) endocrine therapy in patients with ER-positive, HER2-negative early breast cancer, according to the phase 3 lidERA trial. The trial showed a 30% reduction in the risk of invasive disease recurrence or death with giredestrant. The therapy's efficacy was consistent across various subgroups, with notable benefits in certain demographics. Safety profiles were favorable, with lower discontinuation rates for giredestrant. Interim overall survival data also suggested a numerical advantage for giredestrant.

Giredestrant Improves Outcomes in ER+/HER2– Breast Cancer  

Progression-free survival was not statistically significant with Trodelvy versus chemotherapy as first-line treatment in HR+/HER2– metastatic breast cancer.

Among patients with hormone-receptor-positive/HER2-negative breast cancer, progression-free survival (PFS) was not statistically significant with Trodelvy (sacituzumab govitecan-hziy) after endocrine therapy versus chemotherapy, according to updated results from the phase 2 ASCENT-07 study presented at the 2025 San Antonio Breast Cancer Symposium (SABCS).

The median PFS by blinded independent central review in the Trodelvy arm was 8.3 months versus 8.3 months in the chemotherapy arm. At six months, the PFS rate was 71% versus 64%, while the 12-month rates were 40% versus 37%, respectively.

The median PFS by investigator assessment was 8.4 months in the Trodelvy arm versus 6.4 months in the chemotherapy arm. The six-month PFS rate was 69% versus 58%, and the 12-month PFS rate was 36% versus 30% between both arms, respectively.

Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with cancer without the disease getting worse. It shows how well a treatment can keep the cancer from growing or spreading.

Overall Survival (OS): The length of time from diagnosis or the start of treatment that a patient is still alive, no matter what happens with the cancer itself. It is often used to understand how effective a treatment is at helping patients live longer.

The overall survival (OS) in the primary analysis had a 27% maturity. The median OS was not reached (NR) in the Trodelvy arm versus NR in the chemotherapy arm. Of note, 61% of patients in the chemotherapy group were given Trodelvy after treatment discontinuation. The investigators noted that while the data were not mature, an early trend was observed favoring Trodelvy over chemotherapy.

“The ASCENT-07 study in participants with hormone receptor-positive/HER2-negative metastatic breast cancer eligible for first [line] chemotherapy did not meet statistical significance for the primary end point of PFS by BICR,” lead study author Dr. Komal Jhaveri, section head of the Endocrine Therapy Research Program, clinical director of Early Drug Development Services, and the Patricia and James Cayns Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, said during the presentation.

A total of 690 patients were randomly assigned to receive either intravenous Trodelvy (456 patients) at 10 mg/kg on days 1, 8 and 21; in the chemotherapy arm (234 patients), the physician gave patients either capecitabine, paclitaxel or nab-paclitaxel.

The data cutoff for the primary PFS analysis was Sept. 15, 2025. At that time, there were 419 PFS events observed with a 61% maturity, and 187 OS events with a 27% maturity. The median duration of follow-up was 15.4 months.

In the Trodelvy arm, the median duration of treatment was 8.3 months versus 6.1 months in the chemotherapy arm. The median relative dose intensity was 86.2% versus 93%.

Any treatment-emergent side effects occurred in more than 99% of patients in the Trodelvy arm versus 97% in the chemotherapy arm, and grade 3 (severe) or higher treatment-emergent side effects in 72% versus 48%. Treatment-emergent serious side effects were noted in 23% versus 15%. Additionally, treatment-emergent side effects leading to discontinuation occurred in 3% versus 7%, dose interruption in 75% versus 46%, dose reduction in 39% versus 38% and death in 2% versus 2%.

Treatment-related side effects were noted in more than 99% of patients in the Trodelvy arm versus 93% in the chemotherapy arm, with grade 3 or higher treatment-related side effects in 68% versus 37%. Treatment-related serious side effects occurred in 16% versus 5% of patients. Additionally, treatment-related side effects leading to death occurred in 1% versus 1%.

“[Trodelvy] remains a standard of care for hormone-receptor–positive/HER2-negative metastatic breast cancer after prior endocrine therapy and chemotherapy based on the phase 3 TROPiCS-02 study,” Jhaveri concluded.

“Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: primary results from ASCENT-07” by Dr. Komal Jhaveri et al., presented at the 2025 San Antonio Breast Cancer Symposium (SABCS); December 9-12, 2025. Abstract GS1-09.

Updated results from the phase 2 ASCENT-07 study indicate that Trodelvy (sacituzumab govitecan-hziy) did not achieve statistically significant progression-free survival (PFS) compared to chemotherapy in hormone-receptor-positive/HER2-negative breast cancer patients post-endocrine therapy. The median PFS was similar between both treatment arms, with Trodelvy showing a slight advantage in investigator-assessed PFS. Overall survival data were immature, but an early trend favored Trodelvy. Despite higher treatment-emergent side effects, Trodelvy remains a standard care option following prior endocrine therapy and chemotherapy, as supported by the phase 3 TROPiCS-02 study.

Progression-free survival was not statistically significant with Trodelvy versus chemotherapy as first-line treatment in HR+/HER2– metastatic breast cancer. 

Trodelvy Not Associated With Significant Progression Improvements in HR+/HER2– mBC

The phase 3 EPCORE FL-1 trial showed that adding Epkinly to Rituxan and Revlimid delivered superior PFS and response rates in follicular lymphoma.

Among patients with relapsed/refractory follicular lymphoma, fixed-duration Epkinly (epcoritamab) plus Rituxan (rituximab) and Revlimid (lenalidomide; R

) was associated with significant improvements in progression-free survival (PFS) and response rates compared with R

Findings from the phase 3 EPCORE FL-1 trial were presented in a press briefing during the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

At a median follow-up of 14.8 months, results showed that the median PFS per independent review committee (IRC) was not estimable with Epkinly plus R

 alone, leading to a 79% reduction in the risk of disease progression or death. The concordance rate was 94% for PFS between IRC and investigator assessment. The estimated 16-month PFS rates were 85.5% and 40.2%, respectively.

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

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

Complete Response (CR) Rate: The percentage of patients whose cancer completely disappears on tests after treatment.

Partial Response (PR) Rate: The percentage of patients whose cancer shrinks significantly—but does not disappear entirely—after treatment.

Stable Disease (SD): When the cancer does not shrink enough to be called a response but also does not grow or spread. It remains “stable.”

Progressive Disease (PD): When the cancer grows or spreads despite treatment.

Overall Survival (OS): How long patients stay alive after diagnosis or the start of treatment, no matter what happens with the cancer.

Neutropenia: A low number of neutrophils, an important white blood cell that fights infection. Neutropenia increases the risk of infections and is a common side effect of some treatments.

Cytokine Release Syndrome (CRS): A reaction that can happen when certain treatments activate the immune system very strongly. It can cause fever, tiredness, and low blood pressure. Doctors monitor and treat CRS carefully.

Thrombocytopenia: A low number of platelets, the blood cells that help stop bleeding. This can lead to easy bruising, nosebleeds, or bleeding that takes longer to stop.

Pyrexia: The medical word for fever—when the body temperature is higher than normal.

Febrile Neutropenia: A combination of fever and neutropenia (low infection-fighting white cells). This is treated as an emergency because the body may not be able to fight infections well.

The Epkinly regimen elicited a 95% objective response rate (ORR) compared with 79% with R

 alone. In the Epkinly arm, the complete response (CR) rate was 83% and the partial response (PR) rate was 12%; one patient had stable disease (SD), 3% of patients had progressive disease (PD) and 2% were not evaluable. In the R

 arm, the CR rate was 50% and the PR rate was 29%; 7% of patients each had SD, PD and were not evaluable.

 is a novel chemotherapy-free, fixed-duration therapy that is suitable for outpatient administration, and we believe sets a new benchmark as standard of care for second-line [and beyond] follicular lymphoma,” lead study author Dr. Lorenzo Falchi of the Lymphoma Service at Memorial Sloan Kettering Cancer Center in New York said in the oral presentation. “We’re happy to see that the FDA granted full approval to [Epkinly] and R

 on Nov. 18, 2025, for [this patient population].”

 is the only second-line alternative to chemoimmunotherapy-based treatment for patients with relapsed/refractory follicular lymphoma. The FDA initially approved Epkinly, a CD3xCD20 bispecific antibody, as a single agent for the treatment of patients with relapsed/refractory follicular lymphoma following at least two lines of systemic therapy.

Early data from the phase 1b/2 EPCORE NHL-2 trial, which evaluated fixed-duration Epkinly plus R

 for relapsed/refractory follicular lymphoma, demonstrated deep and durable responses and a manageable safety profile.

In November 2025, the FDA also approved Epkinly in combination with R

 in relapsed/refractory follicular lymphoma, based on the phase 3 EPCORE FL-1 findings, which is what Falchi presented during the press briefing. In the international, open-label, EPCORE FL-1 trial, patients underwent randomization to receive fixed-duration Epkinly at 48 milligrams (mg) plus R

Epkinly was administered in a three-step-up, two-dosing schedule at 0.16 mg on day 1, 0.8 mg on day 8 and 3 mg on day 15, all in cycle 1. Cycles 2 and 3 were administered weekly, and cycles 4 to 12 were administered every four weeks. Rituxan was given at 375 mg/m

 for five cycles; the agent was given weekly in cycle 1 and every 4 weeks in cycles 2 through 5. Lastly, Revlimid was given at 20 mg for 12 cycles; treatment was given daily in cycles 1 through 12 on days 1 through 21.

The data cutoff date was May 24, 2025, and patients were enrolled between October 2022 and January 2025.

Baseline characteristics showed that the median age was 61 years and 40% of patients were at least 65 years old; 57% of patients were male and 72% were White. Thirty-one percent of patients had an ECOG performance status of 1 to 2, while 83% had Ann Arbor stage 3 to 4 disease. Regarding Follicular Lymphoma International Prognostic Index, the breakdown of scores was 0 to 1 (24%), 2 (32%) and 3 to 5 (44%). Twenty-two percent of patients had bulky disease, consisting of at least 7 cm.

The median time from initial diagnosis to randomization was five years, and the median number of prior lines of therapy was one, with most patients receiving one (59%), two (24%) or at least three (17%). All patients received a prior anti-CD20 antibody and 3% had received prior R

. Forty-one percent of patients experienced disease progression within two years from starting frontline therapy; 34% of patients were refractory to their first-line therapy, and 37% of patients had double-refractory disease.

Additional efficacy data showed that the median DOR with Epkinly plus R

The Epkinly regimen also extended time to next lymphoma treatment (TTNLT); the median was NE (NE-NE) compared with 24.3 months with R

 alone. At 16 months, 92.8% of patients on Epkinly plus R

 remained free from new anti-lymphoma therapy versus 64.9% of those on R

Falchi noted there is a positive trend for OS with the Epkinly arm, which is NE in both arms, adding that there are 10 and 25 events in the Epkinly and R

-alone arms, respectively. Sixteen-month estimates for OS were 95.8% for Epkinly plus R

Regarding safety, any-grade side effects occurred in 100% and 99% of patients on Epkinly plus R

 alone, with grade 3 (severe) or higher side effects at 90% and 68%, respectively. Serious side effects occurred in 56% and 29%, respectively, and side effects that led to treatment discontinuation occurred in 19% and 12% of patients.

Any-grade and grade 3 or higher side effects of clinical interest occurring in at least 20% of patients on Epkinly/R

 alone included infections (77% and 33% versus 53% and 16%), neutropenia (74% and 69% versus 52% and 42%), cytokine release syndrome (any-grade, 35% versus <1%) thrombocytopenia (28% and 9% versus 18% and 6%), pyrexia (24% and <1%; 14% and 1%), rash (24% and 8% versus 22% and 4%) and COVID-19 (22% and 3% vs 13% and 2%).

On the Epkinly arm, 3% of patients discontinued due to neutropenia versus 2% in the R

-alone arm. Febrile neutropenia occurred in 6% and 3% of patients, respectively. Discontinuation rates due to infections occurred in 6% and 1% of patients, respectively.

Two percent and 4% of patients on Epkinly and R

 alone experienced fatal side effects. “Despite these higher rates of [side effects] in the Epkinly and R

 arm, the median relative dose intensity was greater than 90%,” Falchi added.

“Primary phase 3 results from the EPCORE- FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma” by Dr. Lorenzo Falchi et al., 

“Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed/refractory follicular lymphoma (EPCORE FL-1): a global, open-label, randomised, phase 3 trial,” by Dr. Lorenzo Falchi et al., 

“EPKINLY™ (epcoritamab-bysp) injection prescribing information,” FDA; https://tinyurl.com/mrvfmaur

 drives favorable outcomes in relapsed or refractory follicular lymphoma” by Dr. Lorenzo Falchi et al., 

“FDA approves epcoritamab-bysp for follicular lymphoma indications,” news release, FDA; https://tinyurl.com/y8t4hh3a

Epkinly (epcoritamab) combined with Rituxan (rituximab) and Revlimid (lenalidomide; R2) significantly improved progression-free survival (PFS) and response rates in relapsed/refractory follicular lymphoma compared to R2 alone. The EPCORE FL-1 trial demonstrated a 79% reduction in disease progression risk with Epkinly plus R2. The regimen achieved a 95% objective response rate, with a complete response rate of 83%. Despite higher side effect rates, the treatment's efficacy and manageable safety profile led to FDA approval. The trial highlighted Epkinly's potential as a new standard of care.

The phase 3 EPCORE FL-1 trial showed that adding Epkinly to Rituxan and Revlimid delivered superior PFS and response rates.

Epkinly Combo Effective in Second-Line R/R Follicular Lymphoma

“A chemotherapy-free approach should be the new standard for Ph ALL,” Dr. Sabina Chiaretti, from the Sapienza University of Rome in Italy, said during the ASH 2025 press briefing presentation.

A new study suggests that a treatment combination without traditional chemotherapy should become the new standard for adult patients newly diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL).

Results from the phase 3 GIMEMA ALL2820 trial (NCT04722848), presented in a press briefing at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, showed that the combination of Iclusig (ponatinib) and Blincyto (blinatumomab) led to better outcomes compared with the standard approach of Gleevec (imatinib) plus chemotherapy.

Specifically, findings, which were found to be statistically significant, showed that a complete hematologic response (CHR) was observed in 94.3% of patients in the Iclusig plus Blincyto arm compared with 79.4% of those treated with Gleevec plus chemotherapy; 2.5% versus 10.2% of patients died, 0% vs. 1.3% had refractory disease, and 2.8% versus 8.9% of patients were off treatment (

In the Iclusig plus Blincyto group of patients, no molecular responses were reported in 53.2% at the end of their induction treatment versus 29.1% after 2 cycles of Blincyto, a complete molecular response (CMR) in 30.4% versus 51.9%, and positive non-quantifiable (PNQ) in 16.5% versus 19.0%. The overall molecular response was 46.8% versus 70.9%.

In the Gleevec-plus-chemotherapy group, there was no molecular response in 56.4% of patients at the end of induction versus 51.3% after 4 to 6 cycles of chemotherapy, depending on age; 35.9% versus 37.2% had a CMR, 7.7% versus 11.5% had a PNQ, and 43.6% versus 48.7% had overall molecular responses.

Results were compared with previous findings from the D-ALBA trial (NCT02744768; n = 63) and showed that in the experimental arm, the overall molecular response was 26.9% at the end of induction versus 52.4% after 2 cycles of Blincyto therapy.

At a median follow-up of 23.4 months, the event-free survival (EFS) rate in the Iclusig plus Blincyto arm was 90% (range, 86%-95%) compared with 74% (range, 65%-85%) in the control arm (

 = .0015). The overall survival (OS) was 94% (range, 91%-98%) in the Iclusig plus Blincyto arm versus 77% (range, 66%-91%) in the control arm, and 97% (range, 90%-100%) crossed over.

“A chemotherapy-free approach should be the new standard for Ph ALL,” Dr. Sabina Chiaretti from the Sapienza University of Rome in Italy, said during the presentation. “The first results of the phase 3 GIMEMA ALL2820 trial show for the first time, in head-to-head comparison, a significant advantage of a chemotherapy-free, targeted immunotherapeutic-based approach over a tyrosine kinase inhibitor and chemotherapy strategy, with a higher CHR and minimal residual disease response, fewer deaths, and improved EFS and OS.”

Patients were randomly assigned 2:1 to either the experimental arm (n = 158) or the control arm (n = 78). In the experimental arm, if patients were between 18 and 65 years old they were given Iclusig at 45 mg/day for the first 22 days, followed by 30 mg per day until day 70, and followed by 2 cycles of Blincyto plus Iclusig; if patients were 65 years or older, they were given 30 mg of Iclusig per day until day 70 followed by 2 cycles of Blincyto and Iclusig therapy.

In the control arm, if patients were between 18 and 65 years old they were given chemotherapy plus Gleevec for 3 cycles until day 70, followed by cycles 4 to 6 of Gleevec; if patients were 65 years old or older they were given mild chemotherapy plus Gleevec for 3 cycles until day 7, followed by cycle 4 of Gleevec if there was no CHR or MRD response patients could cross over to the experimental arm.

Dr. Chiaretti noted that ongoing studies will further examine this treatment, focusing on detailed molecular monitoring and patient quality of life.

"First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult Ph+ acute lymphoblastic leukemia patients," Sabina Chiaretti, et al. 

A recent study indicates that a chemotherapy-free regimen should become the new standard for adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). The phase 3 GIMEMA ALL2820 trial demonstrated that the combination of Iclusig (ponatinib) and Blincyto (blinatumomab) significantly outperformed the traditional Gleevec (imatinib) plus chemotherapy approach. The new regimen showed higher complete hematologic response rates, fewer deaths, and improved event-free and overall survival rates. Ongoing research will further explore molecular monitoring and patient quality of life.

A new combination of Blincyto and Iclusig provided improved results and stronger responses for patients with Philadelphia chromosome-positive ALL compared with traditional chemotherapy.

Ariana Pelosci

Giredestrant Improves Outcomes in ER+/HER2– Breast Cancer

Trodelvy Not Associated With Significant Progression Improvements in HR+/HER2– mBC

Epkinly Combo Effective in Second-Line R/R Follicular Lymphoma

A New Option Without Traditional Chemotherapy for Ph+ ALL

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