Kyle Doherty

1.34 mg of Fotivda provided decreased tumor size and may be more tolerable than an 0.89-mg dose in RCC: © Axel Kock - stock.adobe.com

Among patients with renal cell carcinoma (RCC), the Food and Drug Administration (FDA)-approved starting dose of 1.34 milligrams (mg) of Fotivda (tivozanib) resulted in greater antitumor activity than a reduced dose of 0.89 mg, while incidence of hypertension were seen to be comparable.

Progression-free survival: The time a patient lives without their disease spreading or worsening.

Best overall response: The best response a patient has to treatment.

Overall survival: The time a patient lives, regardless of disease status.

This was according to results from an integrated efficacy and safety exposure response analysis that included the phase 3 TIVO-1, 

 studies presented at the 2025 ASCO Genitourinary Cancers Symposium.

“[There was a] strong exposure response relationship between cycle 2 [Fotivda] serum [exposures] and progression-free survival [PFS],” Dr. Bradley McGregor, lead study author, wrote in a poster presentation of the data. McGregor is director of Clinical Research for the Lank Center of Genitourinary Oncology, a senior physician as well as Marra Lochiatto Investigator at Dana-Farber Cancer Institute, and an assistant professor of medicine at Harvard Medical School, all in Boston.

When PFS was stratified by Fotivda cycle 2 exposures quartile, data showed that those who received a higher concentration of Fotivda had the longest median PFS of patients examined. Patients with an exposure ranging from 62 to 177 ng/mL had the longest median PFS at 9.7 months and the median PFS was as follows for those with an exposure ranging from 47.9 to 62.0 ng/mL (median PFS, 9.1 months), 38.4 to 47.9 ng/mL (median PFS, 7.3 months) and 13.9 to 38.4 ng/mL (median PFS, 5.6 months).

“A correlation between [Fotivda exposures] and change in tumor size from baseline was also observed,” McGregor wrote. “Patients in the TiNivo-2 combination therapy arm who received 0.89 mg [of Fotivda] are mostly clustered in the lowest [Fotivda exposure] quartile. As [exposure] quartiles of [Fotivda] increase, patients’ tumor size decreases, indicating [a] higher [Fotivda dose] results in an increased tumor response.”

The Fotivda exposure quartile correlations with changes in tumor size and best overall response (BOR) in the tumor size model revealed the following changes in median BOR for those with an exposure ranging from: 62 to 177 ng/mL (median BOR, –23.8), 47.9 to 62 ng/mL (median BOR, –17.3), 38.4 to 47.9 ng/mL (median BOR, –11.7) and 13.9 to 38.4 ng/mL (median BOR, –7.02). The respective groups included 183, 185, 173 and 176 patients.

In TiNivo-2, the lower dose of Fotivda was given in combination with Opdivo (nivolumab), and modeling data also showed that Opdivo did not affect the pharmacokinetics of Fotivda. Additionally, the incidence of any grade or grade 3 (severe) hypertension was not significantly different between patients who received the two doses of Fotivda.

Data Leading to This Exposure Response Analysis

 was approved by the FDA in March 2021 for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies based on data from TIVO-3. Data from the trial showed that the VEGFR TKI elicited a median overall survival (OS) of 16.4 months in patients (175 patients) versus 19.2 months in patients who received Nexavar (sorafenib, 175 patients). The median PFS was 5.6 months versus 3.9 months, respectively. The recommended dose of Fotivda per the prescribing information and FDA approval is 1.34 mg administered once daily with or without food for 21 consecutive days every 28 days until disease progression or unacceptable toxicity.

Fotivda was given at a lower dose of 0.89 mg for 21 days in a 28-day cycle in TiNivo-2 when it was combined with Opdivo, assuming a risk of hypertension. However, the lower-dose regimen did not improve outcomes when compared with Fotivda monotherapy given at the approved 1.34-mg monotherapy dose. A worsened trend for PFS was observed as patients treated with the doublet (171 patients) experienced a median PFS of 5.7 months versus 7.4 months with the monotherapy (172 patients).

“The results from the TiNivo-2 data set further confirmed that rechallenge with immunotherapy does not add benefit and optimal dosing of [Fotivda] provided the highest clinical benefit following progression on immunotherapy … [exposure response] models show that 1.34 mg [of Fotivda] provides greater antitumor activity than 0.89 mg. The hypertension incidence seems to be comparable, [and] these [exposure response] data suggest that a dose of 1.34 mg [of Fotivda] provides a greater decrease in tumor size and maybe more tolerable,” McGregor wrote in conclusion.

“Integrated efficacy and safety exposure response (ER) analysis of tivozanib (TIVO) for the treatment of renal cell cancer (RCC).” By Dr. Bradley McGregor, et al. 

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Articles

The FDA-approved starting dose of Fotivda (tivozanib) at 1.34 mg demonstrates superior antitumor activity compared to a reduced dose of 0.89 mg in renal cell carcinoma (RCC) patients, with comparable hypertension incidence. Analysis from phase 3 studies shows a strong correlation between higher Fotivda exposure and improved progression-free survival (PFS) and tumor response. The combination of Fotivda with Opdivo did not enhance outcomes, confirming the optimal efficacy of the 1.34 mg dose. These findings suggest that the higher dose offers greater clinical benefits without increased hypertension risk.

Researchers showed that 1.34 mg of Fotivda provided decreased tumor size and may be more tolerable than an 0.89-mg dose among patients with renal cell carcinoma.

FDA-Approved Fotivda Dose More Effective Than Reduced Dose in RCC

Nubeqa plus ADT improved rPFS in mHSPC across all disease volumes, cutting the risk of radiological progression or death by 46%.

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), efficacy outcomes were improved following treatment with Nubeqa (darolutamide) in combination with androgen deprivation therapy (ADT) compared with placebo plus ADT irrespective of disease volume, according to findings from the phase 3 ARANOTE trial.

Data from a subgroup analysis of ARANOTE presented during the 

 demonstrated that patients with high-volume disease who received Nubeqa (315 patients) achieved a median radiological progression-free survival (rPFS) of 30.2 months compared with 19.2 months among those who received placebo (157 patients). Patients with low-volume disease achieved a median rPFS of not reached (NR) in the investigational arm (131 patients) versus NR in the control arm (66 patients).

“The phase 3 ARASENS study demonstrated a greater than 30% reduction in the risk of death with the combination of [Nubeqa] plus ADT and docetaxel, which has become a standard of care for the treatment of patients with mHSPC,” Dr. Fred Saad said during a presentation of the data. “In ARANOTE, [Nubeqa] plus ADT significantly improved rPFS, reducing the risk of radiological progression or death by 46%. Volume of disease is a prognostic factor for patients with mHSPC and here we report a post-hoc analysis of ARANOTE to evaluate the efficacy and safety of [Nubeqa] by disease volume.”

Saad is the director of prostate cancer research at the Montreal Cancer Institute, a uro-oncologist in the Urology Department, and a full professor in the Department of Surgery at the Centre Hospitalier de l'Université de Montréal in Canada.

Radiological progression-free survival (rPFS): the time from treatment initiation to radiographic disease progression or death.

ECOG performance status of 0 to 2: a measure of a patient’s daily functioning, where 0 indicates full activity, and 2 indicates the ability to perform self-care but not work.

Visceral metastases: cancer that has spread to organs such as the liver, lungs or brain.

Gleason Score: a grading system that evaluates the aggressiveness of prostate cancer based on microscopic tumor appearance.

Overall survival (OS): the time from diagnosis or treatment start to death from any cause.

Time to initiation of subsequent anticancer therapy: the duration from treatment start to the beginning of the next line of cancer treatment.

Time to metastatic castration-resistant prostate cancer (mCRPC): the time from initial treatment to the development of resistance to hormone therapy with metastases.

Time to prostate-specific antigen (PSA) progression: the duration until a confirmed rise in PSA levels, indicating potential disease progression.

Rates of undetectable PSA: the proportion of patients achieving PSA levels below the detection threshold.

Time to pain progression: the time until a clinically significant worsening of pain related to cancer.

In November 2024, the FDA accepted a supplemental new drug application (sNDA) seeking the approval of Nubeqa plus ADT for the treatment of patients with mHSPC. The sNDA was supported by previous data from ARANOTE. Findings from ARANOTE presented during the 2024 ESMO Congress showed that regardless of disease volume patients who received Nubeqa plus ADT (446 patients) achieved a median rPFS of NR versus 25 months in the placebo arm (223 patients).

Diving Into the ARANOTE Trial and Baseline Characteristics

ARANOTE was a global, double-blind study that enrolled patients with mHSPC who had an ECOG performance status of 0 to 2. Patients were stratified based on the presence of visceral metastases (yes versus no) and receipt of prior local therapy (yes versus no). Eligible patients were randomly assigned 2:1 to receive Nubeqa at a dose of 600 milligrams twice daily or placebo, both in combination with ADT.

The primary end point was rPFS by central blinded review. Secondary end points included overall survival (OS), time to initiation of subsequent anticancer therapy, time to metastatic castration-resistant prostate cancer (mCRPC), time to prostate-specific antigen (PSA) progression, rates of undetectable PSA (less than 0.2 ng/mL), time to pain progression and safety.

In the post-hoc analysis that Saad presented, patients were evaluated based on disease volume per CHAARTED criteria. High-volume disease was defined as the presence of visceral metastases and/or at least four bone lesions with at least one lesion beyond the vertebral bodies and pelvis. Low-volume disease was defined as not meeting the high-volume criteria.

At baseline, the median age of the overall patient population was 70 years. Most patients had a Gleason score of at least 8 at initial diagnosis (68.3%) and de novo metastasis at initial diagnosis (72.5%). The study also included patients with visceral metastases (12%), those who had received prior local therapy (17.9%), and those with an ECOG performance status of 0 (49.8%). The median serum PSA level at baseline was 21.3 ng/mL.

Further Efficacy and Safety Data from the Analysis

Additional findings from the post-hoc analysis showed that patients in the high- and low-volume groups experienced a delayed time to mCRPC with Nubeqa plus ADT versus placebo plus ADT, which was consistent with the benefit observed in the overall population. Patients with high-volume disease in the investigational and control arms achieved a median time to mCRPC of NR versus 12.4 months, respectively. In the low-volume group, the median time to mCRPC was NR versus 19.8 months, respectively.

The addition of Nubeqa to ADT also led to a benefit compared with placebo plus ADT across all secondary end points examined. The greatest benefits were reported in time to initiation of subsequent systemic anticancer therapy in patients with low-volume disease, time to PSA progression in patients with low-volume disease and time to PSA progression in patients with high-volume disease.

“OS results were immature, but suggestive of a benefit with [Nubeqa] versus placebo,” Saad noted.

Evaluable patients with high-volume disease in the Nubeqa arm (304 patients) had undetectable PSA levels 24, 36 and 48 weeks after random assignment at rates of 44%, 48% and 50%, respectively; 55% of these patients achieved undetectable PSA at any time. Comparatively, patients in the placebo arm (148 patients) achieved undetectable PSA at rates of 11%, 13%, 14% and 16%, at the respective time points.

Patients with low-volume disease who received Nubeqa (121 patients) also experienced undetectable PSA levels at higher rates compared with those who received placebo (63 patients) at the 24- (72% versus 17%, respectively), 36- (78% versus 19%) and 48-week (79% versus 19%) time points. Patients experienced undetectable PSA at any time at rates of 83% versus 25%, respectively.

In terms of safety, patients with high-volume disease who received Nubeqa (314 patients) or placebo (156 patients) both experienced any-grade treatment-emergent side effects (TEAEs; 93% versus 91.7%, respectively), grade 3 (severe) or 4 (life-threatening) TEAEs (31.2% versus 31.2%), serious TEAEs (28.3% versus 25.6%) and TEAEs leading to study drug discontinuation (7.3% versus 8.3%). Patients with low-volume disease in the Nubeqa (131 patients) and placebo (65 patients) arms also experienced any-grade TEAEs (86.3% versus 86.2%), grade 3 or 4 TEAEs (29.8% versus 26.2%), serious TEAEs (12.2% versus 18.5%) and TEAEs leading to study drug discontinuation (3.1% versus 10.8%).

“Efficacy outcomes with [Nubeqa] plus ADT were improved versus placebo plus ADT regardless of disease volume,” Saad said in conclusion. “[Nubeqa] plus ADT was well tolerated in both high-volume and low-volume subgroups with low treatment discontinuation rates consistent with the overall population and reconfirming the established tolerability of darolutamide. Patients with low-volume mHSPC had marked treatment efficacy with minimal treatment burden.”

“Darolutamide plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC) by disease volume: subgroup analysis of the phase 3 ARANOTE trial.” By Dr. Fred Saad, et al. 

“Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial.” By Dr. Fred Saad, et al. 

Nubeqa (darolutamide) combined with androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to placebo plus ADT, regardless of disease volume. The ARANOTE trial demonstrated a 46% reduction in the risk of radiological progression or death. High-volume disease patients achieved a median rPFS of 30.2 months, while low-volume disease patients' rPFS was not reached. Nubeqa plus ADT was well tolerated, with low treatment discontinuation rates, confirming its established safety profile.

Nubeqa plus ADT improved rPFS in mHSPC regardless of disease volume, reducing the risk of radiological progression or death by 46%, per ARANOTE data.

Nubeqa Plus ADT Effective in mHSPC Regardless of Disease Volume

Monjuvi plus Revlimid and Rituxan demonstrated improved progression-free survival for patients with relapsed or refractory follicular lymphoma, as presented at the 2024 ASH annual meeting. 

For patients with relapsed or refractory follicular lymphoma, Monjuvi (tafasitamab-cxix) in addition to Revlimid (lenalidomide) and Rituxan (rituximab) led to a 57% reduction in the risk of disease progression or death versus the placebo plus Revlimid and Rituxan, according to findings from a phase 3 trial that were presented at the 

At a median follow-up of 14.1 months, the median investigator-assessed progression-free survival (PFS) was 22.4 months with the triplet (273 patients) versus 13.9 months with Revlimid and Rituxan alone (275 patients).

According to independent review committee (IRC) assessment, the median PFS was not yet reached with the triplet versus 16 months with the doublet.

“The inMIND phase 3 study met its primary end point of prolonging PFS in relapsed/refractory follicular lymphoma,” Dr. Laurie H. Sehn, lead study author of BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, in Vancouver, Canada, said in a presentation of the data. “Benefit was observed in all prespecified subgroups, including patients with POD24 [progression of disease within 24 months of initial diagnosis], [those who were] refractory to prior anti-CD20 monoclonal antibodies, and [those] receiving multiple prior lines of therapy.”

Progression-free survival (PFS): time patients live without their cancer worsening or spreading.

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

Intravenous: treatment given through the vein.

Additional efficacy findings from the subgroup analysis also illustrated a PFS benefit favoring the investigational regimen regardless of POD24 status and refractoriness to anti-CD20 antibody therapy. In patients with POD24, the median PFS was 19.2 months with the triplet versus 11.3 months with the doublet. In patients without POD24, the median PFS was 23.6 months versus 16 months with the triplet and doublet, respectively.

In patients who were refractory to anti-CD20 antibody therapy the median PFS was 15 months in the investigational arm versus 8.6 months in the control arm. In patients who were not refractory to anti-CD20 antibody therapy the median PFS was 24 months versus 18.2 months with the investigational and control regimens, respectively.

With respect to response in the FDG-avid population the PET-CR rate was 49.4% in the investigational arm (251 patients) versus 39.8% in the control arm (254 patients). In the intention-to-treat population, the objective response rate (ORR) was 83.5% in the triplet arm versus 72.4% in the doublet arm.

Additional efficacy findings demonstrated that the median duration of response (DOR) was 21.2 months with the triplet versus 13.6 months with the doublet.

The median time to next treatment (TTNT) was not reached with the triplet versus 28.8 months with the doublet.

“The safety profile was manageable and consistent with expected toxicities with these agents,” Sehn said, turning to the regimen’s toxicity profile. 

Some of the most common any-grade treatment-emergent adverse effects (TEAEs, side effects) in the Monjuvi and placebo arms, respectively, included neutropenia (48.5%; 45.2%), diarrhea (37.6%; 28.3%), COVID-19 (31.4%; 23.5%), constipation (29.2%; 24.6%), rash (21.9%; 21.3%) and fatigue (21.2%; 15.8%). The most common grade 3 (severe) or 4 (life-threatening) TEAEs in the Monjuvi and placebo arms, respectively, included neutropenia (39.8%; 37.5%), pneumonia (8.4%; 5.1%), thrombocytopenia (6.2%; 7.4%) and decreased neutrophil (white blood cell) count (5.8%; 6.6%), among others. 

Sehn stated that Monjuvi and placebo dose interruptions or discontinuations because of TEAEs were similar between treatment arms, as were discontinuations for Revlimid.

Deaths occurred in 5.5% (15 patients) of patients in the investigational arm versus 8.5% (23 patients) of those in the placebo arm.

Most patients with follicular lymphoma will require more than one line of therapy, and although immunotherapy is a preferred regimen for patients with relapsed or refractory disease, the DOR of these agents remains limited.

The combination of Revlimid and Rituxan has been an FDA-approved regimen for patients with previously treated follicular lymphoma since 2018. The approval was based on data from the phase 3 AUGMENT trial, which showed an improvement in PFS versus Rituxan alone. Monjuvi is a CD19-directed monoclonal antibody that induces direct cytotoxic effects and improves NK cell and macrophage immune-mediated mechanisms.

A total of 548 patients were randomly assigned to treatment with Monjuvi (273 patients) or placebo (275 patients), and 51 (18.7%) and 42 (15.3%) remain on treatment, respectively. A total of 244 (89.4%) and 229 (83.3%) patients in the investigational and control arms, respectively, remain ongoing in the study. At the time of the analysis the median number of cycles received was 12 with Monjuvi versus 11 with placebo.

To be eligible for enrollment patients at least 18 years of age needed to have grade 1 to 3A follicular lymphoma or MZL and received at least one prior line of therapy, including an anti-CD20 monoclonal antibody. An ECOG performance status of 0 to 2 and no prior exposure to Revlimid plus Rituxan were also required.

Following confirmation of eligibility patients were randomly assigned to the experimental or control arm. In the experimental arm patients received 12 milligrams per kilogram (mg/kg) of intravenous (IV) Monjuvi every week for the first three cycles followed by every two weeks for cycles four through 12; plus 20 mg per day of oral Revlimid on days 1 to 21 for 12 cycles; and 375 mg per square meter of IV Rituxan once weekly for the first cycle and every four weeks for cycles two through five. In the control arm patients received IV placebo in the same schedule as Monjuvi, plus Revlimid and Rituxan via the same dosing schedule as the experimental arm.

“This study is the first to validate the approach of combining two antibodies for the treatment of patients with follicular lymphoma. [Monjuvi] plus [Revlimid] and [Rituxan] can be administered in community as well as academic settings and represents a potential new standard of care for patients with relapsed/refractory follicular lymphoma,” Sehn said in conclusion.

“Tafasitamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma: results from a phase 3 study (inMIND).” By Dr. Laurie H. Sehn, 

Monjuvi (tafasitamab-cxix), combined with Revlimid (lenalidomide) and Rituxan (rituximab), significantly reduced the risk of disease progression or death in relapsed/refractory follicular lymphoma patients by 57% compared to placebo plus Revlimid and Rituxan. The phase 3 inMIND trial demonstrated prolonged progression-free survival (PFS) across all subgroups, including those with POD24 and refractory to anti-CD20 therapy. The investigational regimen showed a favorable safety profile, with manageable adverse effects. This combination may establish a new standard of care for relapsed/refractory follicular lymphoma.

Monjuvi plus Revlimid and Rituxan demonstrated improved progression-free survival for patients with relapsed or refractory follicular lymphoma.

Monjuvi Combination May Improve Survival in Follicular Lymphoma

A phase 3b/4 trial evaluated health-related quality of life in patients with HER2-positive breast cancer, regardless of the presence of brain metastases.

In patients with HER2-positive metastatic breast cancer, health-related quality of life (HRQOL) and neurological function data were relative to the efficacy and safety profile of Enhertu (fam-trastuzumab deruxtecan-nxki) regardless of the presence of stable or active brain metastases, according to findings from a phase 3b/4 trial.

The DESTINY-Breast12 trial, which was presented during the 

, deterioration-free rates were evaluated. This included cognitive, emotional, physical, role and social functioning abilities.

At the February 8, 2024, data cutoff, the estimated 12-month deterioration-free rate in terms of global health status (GHS)/QOL was 40.3% among 146 evaluable patients with brain metastases. The estimated 12-month deterioration-free rates in terms of cognitive (119 patients), emotional (92 patients), physical (113 patients), role (135 patients) and social functioning (118 patients) were 53.5%, 63.3%, 56.8%, 44.5% and 54.3%, respectively. The estimated 12-month rates regarding pain (113 patients), fatigue (152 patients) and nausea or vomiting (137 patients) were 53.4%, 40.2% and 46.2%, respectively.

Health-related quality of life (HRQOL): physical and mental well-being over time.

Progression-free survival (PFS): time without cancer progression.

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

Central nervous system PFS: time without cancer progression in the brain or spinal cord.

Patients with stable brain metastases (87 patients) experienced an estimated 12-month deterioration-free rate of 41% in terms of GHS/QOL. The estimated 12-month deterioration-free rates in terms of cognitive (71 patients), emotional (59 patients), physical (65 patients), role (79 patients and social functioning (72 patients) were 55.3%, 59.3%, 58.4%, 44.3% and 52%, respectively. The estimated 12-month rates regarding pain (67 patients), fatigue (89 patients) and nausea or vomiting (78 patients) were 52.8%, 40.3% and 49.5%, respectively.

Patients with active brain metastases (59 patients) had an estimated 12-month deterioration-free rate of 39.2% in terms of GHS and QOL. The estimated 12-month deterioration-free rates in terms of cognitive (48 patients), emotional (33 patients), physical (48 patients), role (56 patients) and social functioning (46 patients) were 50.9%, 70.1%, 54.6%, 45% and 57.8%, respectively. The estimated 12-month rates in terms of pain (46 patients), fatigue (63 patients) and nausea or vomiting (59 patients) were 54.2%, 39.7% and 41.3%, respectively.

The median treatment duration among all patients with brain metastases (263 patients) was 11.5 months, and 118 patients were still receiving Enhertu at the data cutoff.

“Estimated deterioration-free rates at 12-months were above 50% for cognitive, emotional, physical, and social functioning, [as well as] pain scores, regardless of the presence or absence of stable/active baseline brain metastases; further, the majority of patients had neurological stability at first score post baseline [86.6%], which was maintained throughout treatment in 55.1% of patients in the baseline brain metastases cohort and 72.9% of patients without baseline brain metastases,” Dr. Nadia Harbeck and coauthors wrote in a poster presentation of the data.

Harbeck is the director of the Breast Center, as well as the chair for Conservative Oncology and the head of the Oncological Therapy & Clinical Trials Unit in the Department of OB&GYN at LMU University Hospital in Munich, Germany.

 to Enhertu for the treatment of patients with unresectable or metastatic HER2-positive breast cancer following 2 or more prior anti-HER2–based regimens in the metastatic setting. The approval was supported by findings from the phase 2 DESTINY-Breast01. The agent 

 in May 2022 for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received an anti-HER2–based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within 6 months of therapy completion. That approval was based on findings from the phase 3 DESTINY-Breast03 trial.

DESTINY-Breast12 was a study that examined Enhertu in adult patients with HER2-positive metastatic breast cancer with or without baseline brain metastases.To be eligible, patients were allowed to receive up to two prior lines of therapy for metastatic brain cancer, excluding Tukysa (tucatinib). Other key inclusion criteria consisted of disease progression on prior HER2-directed regimens, an ECOG performance status of 1 or less, and no known or suspected leptomeningeal metastases.

Patients were divided into two cohorts: those with baseline brain metastases and those without (241 patients). Both cohorts received intravenous Enhertu at a dose of 5.4 milligram per kilogram every three weeks.

The primary end points were progression-free survival (PFS) in the brain metastases cohort and objective response rate (ORR). Secondary end points included central nervous system (CNS) PFS, time to progression, duration of response, overall survival, safety, HRQOL and neurological function.

Primary findings from DESTINY-Breast12 demonstrated that the 12-month PFS rates among all patients with brain metastases (263 patients), those with stable brain metastases (157 patients), and those with active brain metastases (106 patients), were 61.6%, 62.9% and 59.6%, respectively. The median PFS in the overall population was 17.3 months. The 12-month CNS PFS rates were 58.9%, 57.8% and 60.1%, for all patients with brain metastases, patients with stable brain metastases, and patients with active brain metastases, respectively. The respective confirmed ORRs were 51.7%, 49.7% and 54.7%.

Additional findings from the QOL analysis showed that the estimated 12-month deterioration-free rate in terms of GHS/QOL was 44.3% in evaluable patients without baseline brain metastases (128 patients).The estimated 12-month deterioration-free rates in terms of cognitive (112 patients), emotional (74 patients), physical (101 patients), role (128 patients) and social functioning (112 patients) were 54.9%, 69.1%, 61.3%, 45.3% and 51.1%, respectively. The estimated 12-month rates regarding pain (94 patients), fatigue (142 patients) and nausea/vomiting (143 patients) were 61.2%, 38.3% and 38.6%, respectively. The median treatment duration in the cohort of patients without brain metastases was 12 months.

Most patients without brain metastases (91.9%) had neuroglial stability at first score post baseline. Neuroglial stability was maintained throughout treatment in 72.9% of patients.

“Effects of trastuzumab deruxtecan (Enhertu ) on health-related quality of life (HRQOL) & neurological function in patients (pts) w/ HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINY-Breast12(DB-12) results” by Nadia Harbeck, et al. Presented at: San Antonio Breast Cancer Conference; December 10-13, 2024; San Antonio, TX. Abstract PS14-10.

Enhertu (fam-trastuzumab deruxtecan-nxki) demonstrated efficacy in maintaining health-related quality of life (HRQOL) and neurological function in patients with HER2-positive metastatic breast cancer, regardless of brain metastases status. The DESTINY-Breast12 trial showed that 12-month deterioration-free rates for cognitive, emotional, physical, and social functioning were above 50%. Progression-free survival (PFS) rates were also favorable, with a median PFS of 17.3 months. Enhertu received FDA approval for treating HER2-positive breast cancer after prior anti-HER2 regimens, based on previous trial results.

Treatment with Enhertu showed favorable outcomes regarding health-related quality of life in patients with HER2-positive breast cancer, regardless of brain metastases.

Kyle Doherty

FDA-Approved Fotivda Dose More Effective Than Reduced Dose in RCC

Nubeqa Plus ADT Effective in mHSPC Regardless of Disease Volume

Monjuvi Combination May Improve Survival in Follicular Lymphoma

Enhertu May Help Preserve Quality of Life in HER2-Positive Breast Cancer

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