Kristi Rosa

Real-world data from the U.S. confirms the effectiveness of Monjuvi for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The real-world effectiveness of Monjuvi (tafasitamab-cxix) in U.S. patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was confirmed, along with factors associated with survival, according to data from a retrospective medical chart review presented at the 

At a median follow-up time of 14.7 months from Monjuvi initiation, the real-world progression-free survival (PFS) with Monjuvi was 11.3 months in the overall population (181 patients), and the real-world overall survival (OS) was 24.8 months. The real-world overall response rate (ORR) to the agent was 73.5%, which comprised a complete response (CR) rate of 23.2% and a partial response (PR) rate of 50.3%. In the patients who achieved a real-world CR or PR with the agent (133 patients), the real-world duration of response (DOR) was 9.6 months.

An analysis showed that factors significantly linked with increased risk of progression included receiving the agent in the third to fifth line (51 patients) versus the second line (130 patients), having Ann Arbor stage 3 to 4 disease (169 patients) versus stage 1 to 2 (10 patients), increasing Charlson Comorbidity Index scores (181 patients) and bulky (36 patients) versus non-bulky (145 patients) disease.

Moreover, factors significantly associated with increased risk of mortality included receiving Monjuvi in the third to fifth line versus the second line, increasing age, ECOG performance status of 2 or higher versus below 2 and bulky versus non-bulky disease.

Progression-free survival (PFS): time without disease worsening.

Overall survival (OS): time until death from any cause.

Overall response rate (ORR): percentage of patients with tumor reduction.

Complete response (CR): no detectable cancer.

Partial response (PR): tumor reduction, but not complete.

Duration of response (DOR): time response lasts.

Stable disease (SD): cancer neither grows nor shrinks.

Ann Arbor stage: system to classify lymphoma spread.

Charlson Comorbidity Index scores: predicts mortality based on comorbidities.

Non-bulky disease: small or no large tumor mass.

ECOG performance status: measures a patient's ability to perform daily activities, with scores from 0 (fully active) to 5 (dead). Higher scores indicate greater impairment.

“The additional follow-up from the initial data collection allowed for a more robust evaluation of the real-world effectiveness of [Monjuvi] in patients with relapsed or refractory DLBCL, predominantly in the community practice setting,” lead study author Dr. Kim Saverno of Incyte Corporation, in Wilmington, Delaware, said in a poster presentation of the data. “These results support a real-world clinical benefit for [Monjuvi], with the greatest benefit observed when [the agent] was received in second versus later lines of therapy.”

Additional treatment outcome data showed that in those who received Monjuvi in the second line (130 patients), the real-world ORR was 78.5%; this was comprised of a CR rate of 27.7% and a PR rate of 50.8%. For this group, the stable disease (SD) rate was 8.5%, the progressive disease (PD) rate was also 8.5%, and 4.6% of patients did not have these data available. In the group of patients who received the immunotherapy in the third line (43 patients), the real-world ORR was 62.8%; this comprised a CR rate of 11.6% and a PR rate of 51.2%. In this subset, the SD and PD rates were 18.6% and 11.6%, respectively; 7% of patients did not have these data available.

In patients who experienced a real-world CR as a best response to Monjuvi (42 patients), the median real-world DOR was 19.2 months. In those who achieved a real-world PR as a best response to the agent (91 patients), the median real-world DOR was 8.5 months.

The CD19-targeted immunotherapy Monjuvi was approved by the FDA in July 2020 for use in combination with Revlimid (lenalidomide) in adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma and who are not candidates to undergo autologous stem cell transplant. To date, few studies have evaluated the agent in a US real-world setting, according to Saverno. She added that data from a real-world study were previously shared, but had a limited follow-up time of 6.5 months, which “precluded robust evaluations of the clinical effectiveness” of the agent.

For patients to be considered eligible for the analysis, they must have started treatment with Monjuvi with or without concomitant Revlimid for relapsed or refractory disease on or following Oct. 21, 2020; be at least 18 years old at the time treatment with the agent was started; and have undergone at least four months of follow-up since treatment started. Those who died during this four-month interval were still permitted. If patients received the agent as part of an interventional clinical trial, they were excluded.

A total of 181 patients were included in the study; 144 of these patients were still alive at last follow-up of initial data collection which had occurred between Feb. 22, 2023, and March 29, 2023. Of those patients, 137 patients had additional follow-up data available and underwent additional data collection between Dec. 18, 2023, and Jan. 31, 2024. A total of 106 patients were alive at last follow-up.

“Over 70% of patients received [Monjuvi] in the second line, and 71% of patients had discontinued [Monjuvi] at the last follow-up, mostly due to disease progression,” Saverno noted. “Over half of the patients were still alive at the last follow-up, and among the patients still alive, half [were] still receiving [Monjuvi] at the time of the most recent follow-up.”

In the 181 total patients, the median age at the time of Monjuvi initiation was 71.1 years. Most patients were White (64.1%), and more than half of patients were male (56.4%). Regarding Ann Arbor stage at time of treatment initiation, 5.5% had stage 1 or 2 disease, 93.4% had stage 3 or 4 disease; this information was unknown for 1.1% of patients. ECOG performance status at the time of treatment initiation was 0 to 1 for 52.5% of patients and 2 or higher for 47.5% of patients. Revised International Prognostic Index for Diffuse Large B-cell Lymphoma was 3 to 5 for 80.5% of patients and 1 to 2 for 19.5% of patients.

“This study is impacted by limitations inherent to real-world studies, such as unobserved and missing data,” Saverno concluded. “The number of participating oncologists was small and thus may not reflect the treatment patterns of all US oncologists managing patients with DLBCL.”

“Real-world effectiveness of tafasitamab (tafa) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in the United States.” By Dr. Kim Saverno et al, 

For more news on cancer updates, research and education, don’t forget to 

subscribe to CURE®’s newsletters here.

Articles

Monjuvi (tafasitamab-cxix) demonstrates real-world effectiveness in U.S. patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with a progression-free survival of 11.3 months and overall survival of 24.8 months. The study highlights the importance of early-line treatment, as second-line therapy shows better outcomes compared to later lines. Factors such as disease stage, comorbidity index, and performance status significantly impact progression and mortality risks. Despite limitations, the study supports Monjuvi's clinical benefit, especially when administered in earlier treatment lines.

The real-world effectiveness of Monjuvi for relapsed or refractory diffuse large B-cell lymphoma in the U.S. was demonstrated, according to data from a retrospective analysis.

Real-World Data May Confirm Monjuvi’s Efficacy in Large B-Cell Lymphoma

Adding camrelizumab to chemotherapy significantly improved pathologic complete response rates in patients with early or locally advanced triple-negative breast cancer compared to chemotherapy alone.

Adding camrelizumab to presurgical chemotherapy significantly improved pathologic complete response (pCR) rates compared with chemotherapy alone in patients with early or locally advanced triple-negative breast cancer (TNBC), according to a phase 3 study.

Data from the phase 3 CamRelief study, presented at the 

2024 San Antonio Breast Cancer Symposium (SABCS)

, showed that in all patients, the camrelizumab regimen (222 patients) elicited a pCR rate of 56.8% versus 44.7% with chemotherapy alone (219 patients), translating to a 12.2% difference between the treatment groups.

Notably, pCR benefits with the addition of camrelizumab proved to be generally consistent across the subgroups examined, including higher-risk categories. Specifically, in patients with stage 3 disease, camrelizumab plus chemotherapy (79 patients) induced a pCR rate of 49.4% versus 38.0% with chemotherapy alone (79 patients), translating to an 11.4% difference between the arms. In those with node-positive disease who received the camrelizumab combination (154 patients) or chemotherapy alone (157 patients), the respective pCR rates were 57.8% and 42.7%, translating to a difference of 15.1% between the groups.

Early trends in event-free survival (EFS), disease-free survival (DFS) and distant disease-free survival complemented the pCR benefit observed with camrelizumab plus chemotherapy.

Pathologic complete response (pCR): patients who no longer show signs or symptoms of cancer.

Event-free survival (EFS): time patients remain free of cancer events, including progression or complications.

Disease-free survival (DFS): time patients live without signs or symptoms of cancer after treatment.

Distant disease-free survival: time after treatment when patients live without signs of cancer spreading to distant regions in the body.

ECOG performance status: a measurement of how independently patients can complete tasks. A score of 0 means they can complete tasks entirely independently and a score of 4 means they cannot complete tasks independently.

Objective response rate (ORR): percentage of patients who have a complete or partial response to treatment.

“Our data support camrelizumab plus chemotherapy as a potential new neoadjuvant (presurgical) therapeutic option for treating early or locally advanced TNBC,” Dr. Zhi-Ming Shao of Fudan University Shanghai Cancer Center and Key Laboratory of Breast Cancer, Shanghai Medical College, Fudan University, in China, said in a presentation of the data.

Approximately 15% of all breast cancer cases are triple-negative, and this disease subtype is known to have higher recurrence and poor survival outcomes. For those with early TNBC, the standard treatment approach has been an anthracycline paired with cyclophosphamide (AC), followed or preceded by a taxane. Dose-dense AC has proven effective in significantly reducing recurrence and mortality in these patients, according to Shao. However, the incorporation of platinum into the regimen has led to better pCRs. Despite the progress made to date, new approaches are needed to further improve outcomes.

The phase 3 CamRelief study enrolled patients with stage 2 or 3 invasive TNBC who had not previously received systemic treatment and who had an ECOG performance status of 0 or 1.

Study participants were randomly assigned to receive neoadjuvant camrelizumab or placebo paired with chemotherapy. Both treatment groups received nab-paclitaxel plus carboplatin, followed by epirubicin plus cyclophosphamide. Patients from both groups then went on to surgery, and for adjuvant (postsurgical) treatment, they received camrelizumab plus standard of care (SOC) or SOC per clinical practice guidelines. Xeloda (capecitabine) was allowed in this phase.

The primary end point of the study was pCR rate and secondary end points included EFS, DFS, DDFS, pre-surgery objective response rate (ORR) and safety.

Of the total 563 patients who were screened for eligibility, 441 patients were randomly assigned, including 222 patients assigned to camrelizumab plus chemotherapy and 219 assigned to chemotherapy alone. In the camrelizumab plus chemotherapy group, 196 patients completed treatment with camrelizumab plus nab-paclitaxel and carboplatin, 170 completed camrelizumab plus epirubicin and cyclophosphamide, 167 completed all prespecified neoadjuvant treatments and 198 underwent surgery. In the chemotherapy alone, these respective numbers were 198, 177, 173 and 200 patients.

A total of 222 patients in the camrelizumab combination group and 219 patients in the chemotherapy-alone group were included in the primary analysis. The data cutoff date was September 30, 2023, and the median follow-up time was 14.4 months.

Regarding baseline characteristics, the median age across the camrelizumab-chemotherapy and placebo-chemotherapy groups was 49 years and 48 years, respectively, and most patients had an ECOG performance status of 0 (87.4% versus 86.3%).

Camrelizumab plus chemotherapy led to an ORR of 87.4%, which comprised a complete response (CR) rate of 19.8% and a partial response (PR) rate of 67.6%; 3.2% of patients had stable disease (SD) and 1.4% experienced progressive disease (PD). A total of 8.1% of patients in this arm were not evaluable. Chemotherapy alone induced an ORR of 82.6%, which comprised CR and PR rates of 18.7% and 63.9%, respectively; the SD rate was 6.8% and the PD rate was 4.6%. A total of 5.9% of these patients were not evaluable.

The safety profile was manageable and consistent with the known profiles of each agent, Shao noted.

The mean number of treatment cycles with camrelizumab or placebo was 6.8 and 7.2, respectively. Any-grade side effects occurred in 99.5% of those in the camrelizumab group versus 100% of those in the chemotherapy-alone group. Side effects were grade 3 (severe) or higher for 89.2% and 83.1% of patients, respectively. Two patients in the camrelizumab-chemotherapy group experienced death in the form of interstitial lung disease (one patient) and sudden cardiac death (one patient). Serious side effects occurred in 34.7% and 22.8% of patients, respectively.

Side effects led to treatment discontinuation of any drug in 18.5% of those in the camrelizumab-chemotherapy group and 5.9% of those in the chemotherapy-alone group. In the camrelizumab group, side effects led to discontinuation of camrelizumab (9.9%), nab-paclitaxel (7.7%), carboplatin (10.8%), epirubicin (5.4%) and cyclophosphamide (5.4%); these respective percentages in the chemotherapy-alone group were 2.3%, 2.3%, 3.7%, 2.3% and 2.3%. Immune-related side effects were reported in 92.3% of those in the camrelizumab group versus 16.4% of those in the chemotherapy-alone group. These effects were grade 3 or higher in 9.5% and 0.5% of patients, respectively.

The most common blood-related side effects of any grade experienced by at least 20% of patients in either the camrelizumab or chemotherapy-alone groups included decreased white blood cell count (94.1% versus 97.3%), decreased neutrophil count (93.7% versus 96.3%), anemia (89.6% versus 85.8%), decreased platelet count (64% versus 56.2%) and decreased lymphocyte count (30.6% versus 31.1%).

The most common non-blood-related side effects experienced by at least 20% of patients in the camrelizumab and chemotherapy-alone groups, respectively, comprised reactive capillary endothelial proliferation (87.8% versus 68.9%), increased alanine aminotransferase level (68.5% versus 63.9%), increased aspartate aminotransferase level (62.6% versus 63.9%), alopecia (57.2% versus 52.5%), nausea (45.5% versus 40.6%), vomiting (44.6% versus 44.3%), hypertriglyceridemia (36% versus 34.7%), pyrexia (29.7% versus 20.5%), urinary tract infection (27.9% versus 17.4%), hypercholesterolemia (25.2% versus 22.4%), increased gamma-glutamyltransferase (24.8% versus 24.7%), asthenia (23.9% versus 23.7%) and decreased weight (23.4% versus 11%).

“Neoadjuvant camrelizumab plus chemotherapy for early or locally advanced triple-negative breast cancer (CamRelief): a randomized, double-blind, phase 3 trial” by Zhi-Ming Shao, et al. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract GS-306.

Camrelizumab, when added to presurgical chemotherapy, significantly enhances pathologic complete response (pCR) rates in early or locally advanced triple-negative breast cancer (TNBC) compared to chemotherapy alone. The phase 3 CamRelief study demonstrated a 12.2% increase in pCR with camrelizumab, consistent across various subgroups, including stage 3 and node-positive patients. The study also indicated early positive trends in event-free, disease-free, and distant disease-free survival. While the safety profile was manageable, camrelizumab was associated with higher rates of immune-related side effects and treatment discontinuation.

Presurgical camrelizumab plus chemotherapy significantly improved responses versus chemotherapy alone in early or locally advanced TNBC.

Camrelizumab Plus Chemo May Be New Presurgical Option in Breast Cancer Subset

Treatment with patritumab deruxtecan with or without Femara demonstrated similar treatment responses when compared with multiagent chemotherapy. 

Patients with high-risk, hormone receptor (HR)-positive, HER2-negative breast cancer treated with presurgical patritumab deruxtecan (HER3-DXd) with or without Femara (letrozole) experienced similar responses, including pathologic complete response (pCR) and objective response rate (ORR) compared to multiagent chemotherapy, but with a lower occurrence of severe or worse treatment-related side effects, study results have shown.

Primary results from the phase 2 SOLTI VALENTINE trial presented during the 

 showed that the antibody-drug conjugate (ADC; 50 patients) elicited a pCR rate of 4% and an ORR of 70%. When paired with Femara (48 patients), the pCR rate was 2.1% and the ORR was 81.3%; one patient experienced progressive disease (PD). With standard multiagent chemotherapy (24 patients), the pCR rate was 4.2% and the ORR was 70.8%; one patient had PD. In the total population of 122 patients, the pCR rate was 3.3%, and the ORR was 74.6%; two patients had PD.

Pathologic complete response (pCR): the disappearance of cancer.

Objective response rate (ORR): patients who responded partially or completely to cancer.

Interstitial lung disease: scarring of the lung tissue.

Stomatitis: inflammation and sores in the mouth.

Increased transaminase levels: an indication of liver damage.

Neutropenia: a low count of neutrophils, a type of white blood cell.

Anemia: a low count of healthy red blood cells.

Lymphopenia: low levels of lymphocytes, a type of white blood cell.

Thrombocytopenia: a low count of platelets.

Leukopenia: a low count of white blood cells known as leukocytes.

Febrile neutropenia: when a patient with neutropenia experiences a fever.

Moreover, patritumab deruxtecan demonstrated biological evidence of antitumor activity, with a drop in Ki67, a switch to less proliferative PAM50 subtypes, and a decrease in risk of recurrence (ROR). The ADC also led to an increase in CelTIL score that correlated with treatment response.

“SOLTI VALENTINE supports the effectiveness of [patritumab deruxtecan] in early breast cancer and its potential incorporation in the treatment of high-risk HR-positive/HER2-negative breast cancer,” Dr. Mafalda Oliveira of Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, and of the SOLTI Cancer Research Group, both in Barcelona, Spain, said in a presentation of the data.

It is known that multiagent chemotherapy regimens boost survival outcomes for this population, but a need remains for not only effective, but tolerable, therapeutic approaches. The first-in-class, HER3-directed ADC patritumab deruxtecan has demonstrated activity in several subtypes of breast cancer.

Based on these observations, investigators hypothesized that patritumab deruxtecan monotherapy or in combination with Femara would be a safe and effective neoadjuvant option for treatment-naive patients with high-risk, HR-positive, HER2-negative early breast cancer.

To test this, they launched the parallel, randomized, noncomparative, open-label, phase 2 SOLTI VALENTINE trial, which sought to enroll 120 pre- and postmenopausal patients with primary operable breast cancer of 1 centimeter or larger by MRI. To be eligible, patients needed to have HR-positive, HER2-negative disease, as well as a Ki67 expression of 20% or higher and/or high genomic risk. They could not have previously received treatment for their current breast cancer. They also needed to have pretreatment formalin-fixed paraffin-embedded core-needle biopsy.

Patients were randomly assigned to receive patritumab deruxtecan at 5.6 milligrams per kilogram (mg/kg) every 21 days for six cycles; patritumab deruxtecan at the same dose plus Femara at 2.6 mg once daily with or without ovarian function suppression; or standard multiagent chemotherapy in the form of epirubicin at 90 mg/per square meter plus cyclophosphamide at 600 mg/ per square meter or doxorubicin at 60 mg/m

 plus cyclophosphamide at 600 mg/per square meter for four cycles followed by weekly paclitaxel at 80 mg/ per square meter for 12 weeks. Patients were stratified by axillary nodal status. Patients then went on to surgery and will be followed for five years.

Patients were recruited between November 2022 and September 2023. A total of 154 patients were assessed for eligibility, and 32 were excluded due to withdrawn consent (eight patients), metastatic disease (nine patients), no pretreatment biopsy (two patients) and other (13 patients). A total of 122 patients were included in the analysis; 50 received the ADC alone, 48 received the doublet and 24 received chemotherapy; 49, 48 and 23 patients, respectively, went on to surgery. The data cutoff date for the analysis shared during the meeting was April 22, 2024.

In the overall population, the median age was 51 years, and 99.2% were female. About half (52.9%) were premenopausal, and most had lymph node positivity (76.2%). More than half of patients had stage 2 disease (64.0%) and grade 1 or 2 disease (78.4%).

Regarding safety, any-grade treatment-related side effects occurred in 96% of those in the ADC-alone arm (50 patients), 97.9% of those in the ADC/Femara arm (48 patients) and 95.8% of those in the chemotherapy arm (24 patients); they were grade 3 or higher in 14%, 14.6% and 45.8% of patients, respectively. In the ADC-alone arm, dose reduction and interruption were needed for 6% and 12% of patients, respectively. No patients in this arm experienced treatment-related side effects that led to treatment discontinuation. In the ADC/Femara arm, dose reduction, interruption and treatment discontinuation was needed for 8.3%, 4.2% and 4.2% of patients, respectively; in the chemotherapy arm, these respective rates were 37.5%, 50% and 8.3%.

No cases of interstitial lung disease were reported, and no treatment-related deaths occurred. However, one non-related death occurred in the ADC arm due to a cerebrovascular accident.

The most common non-hematologic treatment-related side effects reported in 20% or more of patients in the ADC-alone, ADC/Femara and chemotherapy arms included fatigue (50%; 68.8%; 79.2%), nausea (56%; 72.9%; 58.3%), alopecia (52%; 68.8%; 45.8%), diarrhea (42%; 54.2%; 8.3%), stomatitis (14%; 18.8%; 41.7%), increased transaminase levels (14%; 37.5%; 20.8%), neurotoxicity (0%; 0%; 33.3%), abdominal pain (16%; 29.2%; 8.3%), constipation (20%; 29.2%; 8.3%) and vomiting (22%; 22.9%; 8.3%).

The most common hematologic treatment-related side effects in the respective arms included neutropenia (26%; 18.8%; 41.7%), anemia (12%; 14.6%; 33.3%), lymphopenia (2%; 4.2%; 8.3%), thrombocytopenia (2%; 4.2%, 12.5%), leukopenia (4%; 0%; 8.3%), and febrile neutropenia (0%; 0%; 4.2%).

“Neoadjuvant HER3-DXd alone or in combination with letrozole for high-risk HR+/HER2- early EBC: Primary results of the randomized phase II SOLTI VALENTINE trial” by Dr. Mafalda Oliveira et al., presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, Texas.

Presurgical patritumab deruxtecan (HER3-DXd), alone or with letrozole, showed comparable efficacy to multiagent chemotherapy in high-risk HR-positive, HER2-negative breast cancer, with lower severe side effects. The phase 2 SOLTI VALENTINE trial reported a pathologic complete response (pCR) rate of 3.3% and an objective response rate (ORR) of 74.6% across 122 patients. Patritumab deruxtecan demonstrated antitumor activity, reducing Ki67 and recurrence risk. Safety profiles favored the ADC, with fewer grade 3 or higher side effects compared to chemotherapy, supporting its potential as a neoadjuvant option.

Patients with high-risk, HR-positive, HER2-negative breast cancer treated with HER3-DXd with or without Femara (letrozole) experienced fewer side effects than with chemotherapy.

HER3-DXd With or Without Femara Effective for Some With High-Risk Breast Cancer

Treatment with imlunestrant improved PFS for patients with ER-positive, HER2-negative advance breast cancer with ESR1 mutations compared with hormone therapy. 

The oral selective estrogen receptor degrader (SERD) imlunestrant improved progression-free survival (PFS) compared with standard-of-care (SOC) endocrine therapy for the treatment of patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer with ESR1 mutations with progression on previous endocrine therapy, according to data from the phase 3 EMBER-3 trial.

The findings, which were presented at the 

, also demonstrated that PFS improvement was not statistically significant in the overall population, which included patients without ESR1 mutations.

In addition, results also showed that the combination of imlunestrant and Verzenio (abemaciclib) improved PFS compared with imlunestrant alone in the overall population of EMBER-3, irrespective of ESR1 mutation status.

Oral selective estrogen receptor degrader: a drug that binds to and breaks down estrogen receptors.

Progression-free survival: the time during and after treatment when a patient with cancer is alive without disease worsening.

Overall survival: the time from diagnosis or the start of treatment when a patient with cancer is still alive.

Overall response rate: the percentage of patients with a complete or partial response to treatment.

Central nervous system progression: the spread of cancer to the brain or spinal cord.

Findings showed that patients with ESR1-mutated disease treated with imlunestrant monotherapy (138 patients) experienced a median PFS of 5.5 months compared with 3.8 months for those given SOC endocrine therapy (118 patients). In the overall population, the median PFS was 5.6 months for imlunestrant monotherapy (331 patients) versus 5.5 months for endocrine therapy (330 patients). Notably, there was no statistical difference in PFS between the two treatment groups for patients without ESR1 mutations.

In the overall population, those treated with imlunestrant plus Verzenio (213 patients) achieved a median PFS of 9.4 months versus 5.5 months for those given imlunestrant alone (213 patients). Notably, the efficacy analysis for imlunestrant monotherapy versus imlunestrant plus Verzenio was confined to the imlunestrant monotherapy population enrolled concurrently with patients in the combination arm.

In patients harboring ESR1 mutations, the median PFS was 11.1 months for imlunestrant plus Verzenio (67 patients) versus 5.5 months for imlunestrant monotherapy (92 patients. In patients without ESR1 mutations, the median PFS was 9.1 months for the combination (146 patients) versus 5.5 months for imlunestrant alone (121 patients.

“Imlunestrant as monotherapy or combined with [Verzenio] provides an all-oral targeted therapy option after progression on endocrine therapy for patients with ER-positive, HER2-negative advanced breast cancer,” lead study author Dr. Komal Jhaveri, said in a presentation of the data. Jhaveri is the section head of the Endocrine Therapy Research Program Clinical, director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, New York.

EMBER-3 Design and Patient Characteristics

EMBER-3 enrolled men and pre- or postmenopausal women with ER-positive, HER2-negative advanced breast cancer. Patients were allowed to enroll if they experienced disease recurrence on or within 12 months of completing adjuvant treatment with an aromatase inhibitor (AI) with or without a CDK4/6 inhibitor, or if they had disease progression after first-line treatment with an AI with or without a CDK4/6 inhibitor in the advanced disease setting. No other prior treatments for advanced breast cancer were permitted.

Patients were randomly assigned to receive imlunestrant alone; SOC endocrine therapy consisting of Faslodex (fulvestrant) or Aromasin (exemestane); or imlunestrant plus Verzenio.

PFS for imlunestrant monotherapy versus endocrine therapy in the ESR1-mutated and overall populations, as well as PFS for imlunestrant plus Verzenio versus imlunestrant alone in the overall population, served as the trial’s main areas of focus. Other areas of interest included overall survival (OS), overall response rate (ORR) and safety. PFS and OS for the combination regimen versus SOC endocrine therapy were exploratory areas of interest.

At data cutoff, 20% of patients in the imlunestrant monotherapy arm remained on treatment. Reasons for treatment discontinuation included progressive disease (PD; 72%), side effects (3%), death (2%), patient withdrawal (1%), and protocol deviation (1%). In the SOC endocrine therapy arm, 13% of patients remained on study treatment; reasons for treatment discontinuation included PD (78%), death (2%), patient withdrawal (3%), protocol deviation (1%) and physician decision (1%). Thirty-five percent of patients in the imlunestrant plus Verzenio arm remained on treatment; reasons for discontinuation comprised PD (53%), side effects (5%), death (2%), patient withdrawal (2%) and physician decision (1%).

PFS data were consistent across subgroups for both imlunestrant monotherapy in the ESR1-mutated population and imlunestrant plus Verzenio in the overall population.

Findings from a subgroup analysis showed that among patients who received a prior CDK4/6 inhibitor, the median PFS was 9.1 months for imlunestrant plus Verzenio (139 patients) versus 3.7 months for imlunestrant monotherapy (140 patients). Patients harboring a mutation in the PI3K pathway treated with the combination (88 patients) experienced a median PFS of 7.6 months versus 3.8 months for those given imlunestrant monotherapy (84 patients).

Among patients with measurable disease, the investigator-assessed ORR was 12% for imlunestrant (262 patients) versus 8% for endocrine therapy (251 patients) in the overall population. The ORR was 14% for imlunestrant alone (112 patients) versus 8% for endocrine therapy (91 patients) in the ESR1-mutated population; the respective ORRs were 11% and 9% for imlunestrant (150 patients) and endocrine therapy (160 patients) in the population of patients without ESR1 mutations.

The ORR in the overall population was 27% for imlunestrant plus Verzenio (167 patients) versus 12% for imlunestrant alone (169 patients) and 5% for endocrine therapy (162 patients). In the ESR1-mutated population, the ORRs were 35% for the combination (54 patients), 15% for imlunestrant alone (74 patients) and 3% for endocrine therapy (58 patients). In patients without ESR1 mutations, the ORRs for the combination (113 patients), imlunestrant alone (95 patients) and endocrine therapy (104 patients) were 23%, 10% and 6%, respectively.

Data from an exploratory analysis showed that imlunestrant monotherapy was associated with an improvement in central nervous system (CNS) progression. However, Jhaveri explained the data should be interpreted with caution due to the low rate of CNS events. In the ESR1-mutated population, two CNS progression events were reported in the imlunestrant monotherapy arm (138 patients) versus seven events in the endocrine therapy arm (118 patients). In the overall population, five CNS progression events were reported in the imlunestrant arm (331 patients) versus 10 events in the endocrine therapy arm (330 patients).

Safety data showed that any-grade treatment-emergent side effects occurred in 83% of patients in the imlunestrant monotherapy arm (327 patients) versus 84% of patients in the endocrine therapy arm (334 patients). The rates of grade 3 (severe)or higher treatment-emergent side effects were 17% and 21%, respectively. The most common any-grade treatment-emergent side effects reported in at least 10% of patients included fatigue (imlunestrant, 23%; endocrine therapy, 13%), diarrhea (21%; 12%), nausea (17%; 13%), arthralgia (14%; 14%), increased aspartate aminotransferase levels (13%; 13%), back pain (11%; 7%), increased alanine aminotransferase levels (10%; 10%), anemia (10%; 13%) and constipation (10%; 6%).

Serious side effects occurred in 10% of patients in the imlunestrant arm versus 12% of patients in the endocrine therapy arm. In the imlunestrant monotherapy group, side effects led to dose reductions, treatment discontinuation and death in 2%, 4%, and 2% of patients, respectively. These respective rates were 0%, 1%, and 1% in the endocrine therapy group.

In the imlunestrant plus Verzenio arm (208 patients), any-grade and grade 3 or higher treatment-emergent side effects were reported in 98% and 49% of patients, respectively. The most common treatment-emergent side effects reported in at least 20% of patients included diarrhea (any grade, 86%; grade ≥3, 8%), nausea (49%; 2%), neutropenia (48%; 20%), anemia (44%; 8%), fatigue (39%; 5%), vomiting (31%; 1%), leukopenia (26%; 4%), hypercreatinemia (22%; 1%), abdominal pain (20%; 2%) and decreased appetite (20%; 1%). Serious side effects occurred in 17% of patients. Side effects led to dose reductions, treatment discontinuation and death in 39%, 6%, and 1% of patients, respectively.

“The safety profile [of imlunestrant plus Verzenio] was [consistent with] what we know about the [Verzenio] profile, and [it] compared favorably with prior reports Faslodex plus [Verzenio] with no new added safety signal,” Jhaveri concluded.

Imlunestrant, an oral selective estrogen receptor degrader, demonstrated improved progression-free survival (PFS) in patients with ESR1-mutated, ER-positive, HER2-negative advanced breast cancer compared to standard endocrine therapy. The combination of imlunestrant and Verzenio further enhanced PFS across the overall population, regardless of ESR1 mutation status. Safety profiles were consistent with known data, with manageable side effects. The EMBER-3 trial highlighted imlunestrant's potential as a targeted therapy option post-endocrine therapy progression, offering a promising alternative for patients with advanced breast cancer.

Treatment with imlunestrant either with or without Verzenio was shown to improve progression-free survival in some with ER-positive, HER2-negative advanced breast cancer after endocrine therapy.

Kristi Rosa

Real-World Data May Confirm Monjuvi’s Efficacy in Large B-Cell Lymphoma

Camrelizumab Plus Chemo May Be New Presurgical Option in Breast Cancer Subset

HER3-DXd With or Without Femara Effective for Some With High-Risk Breast Cancer

Imlunestrant-Based Therapy May Improve Survival Without Progression in Advanced Breast Cancer

Latest News