Ariana Pelosci

Results from the phase 3 VERONA trial were presented at the 2025 Society of Hematologic Oncology Annual Meeting.

Patients with revised international prognostic scoring system intermediate and high-risk myelodysplastic syndrome (MDS) did not experience an overall survival (OS) improvement from the treatment combination of Venclexta (venetoclax) plus azacitidine when compared with placebo, study results have shown.

In the combination arm, the median OS was 22.18 months versus 21.68 months in the placebo arm. The modified overall response rate (ORR) in the Venclexta/azacitidine arm was 76.2%. The marrow complete response (CR) rate was 57.8%, the partial response (PR) rate was 0.4% and the CR rate was 18%. In the placebo arm, the modified ORR was 57.7%, the marrow CR rate was 37.5% and the CR rate was 20.2%.

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

Overall response rate: patients who responded partially or completely to treatment.

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

Anemia: low count of healthy red blood cells.

Thrombocytopenia: low count of platelets.

The overall hematological improvement in the combination arm was 49.4% compared with 41.2% in the placebo arm. The transfusion independence rates were 55.7% versus 33.6%, respectively. The median duration of transfusion independence was 183 days vs 294 days.

“Subgroup analyses [showed] [Venclexta] plus azacitidine trended toward an mOR benefit versus placebo plus azacitidine for patients with more than 5% to less than 20% bone marrow blasts for ASXL1, TP53 and RUNX1 mutations at baseline,” Dr. Guillermo Garcia-Manero, chair ad interim in the Department of Leukemia, Division of Cancer Medicine, fellowship program director in the Department of Leukemia, and Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research among other titles, at The University of Texas MD Anderson Cancer Center in Houston, said during the presentation.

A total of 509 patients were randomly evenly assigned to either the combination or placebo arms. Patients were given Venclexta at 400 mg by mouth daily on days 1 to 14 plus azacitidine at 75 mg/m

 intravenously or subcutaneously for seven of the first nine days. The placebo plus azacitidine arm matched the combination arm’s dosing. Patients continued treatment until relapse, progressive disease, hematopoietic stem cell transplant (HSCT) or unacceptable toxicity. Patients then transitioned to follow-up.

The median follow-up was 41.2 months, the median duration of treatment was 6.4 months and the median number of cycles was six.

No new safety signals were observed. The most common any-grade treatment-emergent side effects included neutropenia (77.3% versus 60.2%), thrombocytopenia (66.3% versus 58.9%), anemia (44.7% versus 38.2%) and constipation (42.4% versus 50.4%) between the combination and placebo arms of the trial, respectively.

Serious side effects leading to treatment discontinuation occurred in 41.6% of patients in the combination arm and 55.3% of patients in the placebo arm, while dose interruption was noted in 78.8% versus 67.9% of patients and dose reduction of Venclexta or placebo was found in in 12.5% versus 6.9% while azacitidine was 48.6% versus 27.2%.

Side effects leading to death included disease progression (1.6% versus 0.8%), septic shock (1.2% versus 0.8%), sepsis (0.4% versus 0.8%) and acute myeloid leukemia transformation (0.4% versus 0.8%) among patients in the combination and placebo arms, respectively. The most common cause of death was disease progression (39.2% versus 40.7%) and side effects (10.6% versus 11.4%).

Garcia-Manero G, Platzbecker U, Fenaux P, et al. Primary analysis of the randomized phase 3 VERONA study of venetoclax plus azacitidine versus placebo with azacitidine in patients with treatment-naïve, intermediate and higher-risk myelodysplastic syndromes. Presented at the 2025 Society of Hematologic Oncology Annual Meeting, Houston, TX; September 3-6, 2025. Abstract MDS-1497.

For more news on cancer updates, research and education, 

don’t forget to subscribe to CURE®’s newsletters here.

Articles

The phase 3 VERONA trial evaluated the efficacy of Venclexta (venetoclax) plus azacitidine in patients with intermediate and high-risk myelodysplastic syndrome (MDS). Results indicated no significant improvement in overall survival compared to placebo. The combination arm showed a higher modified overall response rate and marrow complete response rate. Subgroup analyses suggested potential benefits for specific genetic mutations. Common side effects included neutropenia and thrombocytopenia, with serious side effects leading to treatment discontinuation in a notable percentage of patients. The trial highlighted the need for further research to optimize treatment strategies for MDS.

Results from the phase 3 VERONA trial were presented at the 2025 Society of Hematologic Oncology Annual Meeting.

Venclexta And Azacitidine Fail to Improve MDS Survival

Adding casdatifan to Cabometyx showed encouraging activity and in previously treated ccRCC: © stock.adobe.com.

In patients with previously treated clear cell renal cell carcinoma, a specific kind of kidney cancer, adding casdatifan to Cabometyx (cabozantinib) treatment showed encouraging activity and was generally well tolerated, according to results from an expansion group in the phase 1 ARC-20 trial presented at the 

In the group of patients who received 50 milligrams (mg) of Welireg twice daily (32 patients), at the median follow-up of 15 months, the confirmed overall response rate was 25%. The best overall response rate was 31%; zero patients had a complete response, 31% had a partial response, 50% had stable disease, and 19% had progressive disease.

In patients who received 50 mg once daily (28 patients), at the median follow-up of 12 months, the confirmed overall response rate was 29%. The best overall response rate was 32%; 4% of patients had a complete response, 29% had a partial response, 54% had stable disease, and 14% had progressive disease.

In those who received 100 mg once daily (27 patients), at the median follow-up of five months, the confirmed overall response rate was 33%. The best overall response rate was 33%; 0% of patients had a complete response, 33% had a partial response, 52% had stable disease, and 7% had progressive disease.

Patients who received the 100 mg dose demonstrated a trend of decreasing sum of target lesion diameters as well as rapid response.

Preliminary efficacy from the cohort of patients who received Welireg plus Cabometyx (24 patients) showed, with a median follow-up of 5.3 months, the confirmed overall response rate was 46%; 4% had a complete response, 42% had a partial response, 50% had stable disease, and 4% had progressive disease.

“Treatment with Welireg showed meaningful clinical activity and disease control across doses,” wrote presenting study author, Dr. Toni K. Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, co-leader of the Kidney Cancer Program at Dana-Farber/Harvard Cancer Center and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School, said during the presentation. “Welireg was well tolerated across all monotherapy doses and in combination with Cabometyx.”

In the dose expansion phase of ARC-20, approximately 30 patients were enrolled in each of the 3 cohorts. In cohort 1, patients received 50 mg of Welireg twice daily; in cohort 2, patients received 30 mg of Welireg once daily; and in cohort 3, patients received 100 mg of Welireg once daily. Eligible patients had clear cell renal cell carcinoma, were in at least the second line of therapy, had at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1, and had adequate organ and marrow function.

The median age of patients in cohorts 1, 2, and 3 were 62 years, 65 years, and 60 years; an Eastern Cooperative Oncology Group performance status of 1 was observed in 52%, 42%, and 52%, respectively; the most common International Metastatic Renal Cell Carcinoma Database Consortium risk score was intermediate in 64%, 55%, and 66%; and 2 or more prior regimens were received by 94%, 84%, and 83%. All patients in all cohorts received both a vascular endothelial growth factor receptor–tyrosine kinase inhibitor and a programmed death-ligand 1 inhibitor.

The trial’s primary end points were side effects and dose-limiting toxicities. Secondary end points were overall response rate assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 and pharmacokinetics and pharmacodynamics; exploratory end points were progression-free survival, overall survival, and biomarkers.

With Welireg monotherapy, any treatment-emergent side effect related to the study drug occurred in 94% of cohort 1, 90% of cohort 2, and 93% of cohort 3; of grade 3 or higher occurred in 49%, 32%, and 28%, respectively; and serious side effects occurred in 3%, 10%, and 7%.

Grade 3 or higher side effects that occurred in more than 5% of patients in cohort 1 were anemia (42%) and hypoxia (9%); in cohort 2, they were 32% and 7%; and in cohort 3, they were 17% and 10%.

In patients who received 100 mg of Welireg plus Cabometyx (42 patients), with a median follow-up of 3.7 months, any side effects related to Welireg occurred in 98%, grade 3 or higher side effects occurred in 31%, and serious side effects in 7%. Any side effects related to Cabometyx occurred in 93%, grade 3 or higher side effects occurred in 38%, and serious side effects occurred in 12%. Any side effects related to any study drug occurred in 98%, grade 3 or higher side effects occurred in 48%, and serious side effects occurred in 17%.

In the combination group, side effects related to Welireg were anemia (24%), hypoxia (7%), and decreased neutrophil count (2%); side effects related to Cabometyx were anemia (14%), hyponatremia (7%), hypertension (5%), and decreased neutrophil count (5%); and side effects related to any study drug were anemia (24%), hyponatremia (7%), hypoxia (7%), hypertension (5%), and decreased neutrophil count (5%).

Further, in the monotherapy group, 9% of patients in cohort 1, 3% in cohort 2, and 7% in cohort 3 experienced any side effect leading to dose reduction. In the combination group, side effects leading to dose reduction were related to Welireg in 24%, related to Cabometyx in 38%, and related to any study drug in 52%. It was noted that most patients who had a dose reduction of either agent were reduced by only 1 level.

The phase 3 PEAK-1 trial evaluating 100 mg of daily Welireg plus 60 mg of daily Cabometyx compared with placebo plus Cabometyx in patients with advanced or metastatic clear cell renal cell carcinoma was announced, as well as the phase 1b/3 eVOLVE-RCC02 trial evaluating volrustomig plus Welireg in frontline advanced clear cell renal cell carcinoma.

“Combination casdatifan plus cabozantinib in previously treated patients with clear cell renal cell carcinoma: results from an expansion cohort of ARC-20 (NCT05536141),” by Dr. Toni Chouieri, et al. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA.

For more news on cancer updates, research and education,

The addition of casdatifan to Cabometyx (cabozantinib) in patients with previously treated clear cell renal cell carcinoma demonstrated promising efficacy and tolerability in the phase 1 ARC-20 trial. Different dosing regimens of Welireg were evaluated, with varying response rates and side effect profiles. The combination of Welireg and Cabometyx showed a higher overall response rate compared to monotherapy. The trial's primary endpoints focused on side effects and dose-limiting toxicities, while secondary endpoints included overall response rate and pharmacokinetics. Future trials, such as PEAK-1 and eVOLVE-RCC02, are planned to further investigate these treatments.

Adding casdatifan to Cabometyx therapy showed encouraging activity and was generally well tolerated in previously treated clear cell renal cell carcinoma. 

Welireg Plus Cabometyx Shows Tumor Control in Kidney Cancer Trial 

Data from the KEYNOTE-B61 trial show tumor shrinkage in different types of kidney cancer, including papillary and chromophobe subtypes: © stock.adobe.com.

Updated results from the phase 2 KEYNOTE-B61 trial showed that combining Keytruda (pembrolizumab) with Lenvima (lenvatinib) continued to help shrink tumors and improve survival when used as a first treatment for people with advanced non-clear cell kidney cancer, according to data presented at the 

Among all evaluable patients who received Keytruda plus Lenvima (152 patients), the overall response rate was 50.6%, the disease control rate was 82.3% and the clinical benefit rate was 71.5%. Data showed complete responses in 10.1% of patients and partial responses in 40.5%.

The study treatment yielded an overall response rate of 53.8% in patients with papillary disease (93 patients), 31% in those with chromophobe histology (29 patients) and 66.7% in those with translocations (6 patients). Additionally, 50% and 77.8% of patients with unclassified (20 patients) and other histology (9 patients) experienced a response.

Any reduction in tumor burden occurred in 88.6% of all patients. Tumor burden reductions were observed in 91.4% of those with papillary disease, 75.9% of those with chromophobe histology, 95% of those with unclassified disease, 100% of those with translocations and 88.9% of those with other histologies. The median duration of response was 23.5 months.

The median progression-free survival was 17.9 months across the overall population, which included a progression-free survival rate of 39% at 24 months and 26% at 36 months. Additionally, the median progression-free survival was 17.7 months in the papillary subgroup and 11.3 months in the chromophobe subgroup. In each respective group, the 24-month progression-free survival rate was 35% and 44%, and the 36-month rate was 22% and 27%.

Across the overall population, the study treatment produced a median overall survival of 41.5 months, with overall survival rates of 67% at 24 months and 54% at 36 months. The median overall survival was 37.5 months in the papillary subgroup and was not reached in the chromophobe subgroup. The overall survival rates in each group were 65% versus 69% at 24 months, and 50% versus 62% at 36 months.

“After a minimum of 3 years of follow-up, Keytruda plus Lenvima continued to show durable antitumor activity and promising survival outcomes in the first-line setting for patients with advanced non-clear cell renal cell carcinoma,” lead study author Dr. Laurence Albiges, stated in the presentation. “As of now, this is one of our standards of care to treat patients including papillary, chromophobe or different histologies than non-clear cell renal cell carcinoma. We're excited that this has changed the paradigm for our patients.”

Albiges is head of the Department of Oncology at Institut Gustave Roussy.

In the single-arm KEYNOTE-B61 trial, 158 patients were assigned to receive Keytruda at 400 mg intravenously every 6 weeks for a maximum of 18 cycles plus Lenvima at 20 mg orally once daily.

The trial’s primary end point was overall response rate per blinded independent central review using RECIST 1.1 criteria. Secondary end points included duration of response, progression-free survival, overall survival and safety.

Patients 18 years and older with histologically confirmed stage 4 non-clear cell renal cell carcinoma, measurable disease per RECIST 1.1 guidelines, a Karnofsky performance status of 70% or higher and no prior therapy for advanced disease were eligible for enrollment on the trial. Having adequately controlled blood pressure with or without antihypertensive medications as well as adequate organ function were additional requirements for study entry.

The median patient age was 60 years. The most common histology was papillary (58.9%) followed by chromophobe (18.4%), unclassified (12.7%), other (5.7%), translocated (3.8%) and medullary (0.6%). Additionally, 12% of patients had sarcomatoid features and 63.3% had an intermediate or poor International Metastatic Renal Cell Carcinoma Database Consortium risk.

Investigators administered any subsequent therapy to 38.6% of the study population. The most common types of subsequent treatment included any VEGF or VEGFR inhibitor (35.4%), any mTOR inhibitor (8.9%) and any PD-(L)1 inhibitor (6.3%).

Any-grade side effects affected 99.4% of patients and 77.2% experienced grade 3 to 5 toxicities. Additionally, 31% of side effects resulted in treatment discontinuation, 48.1% had serious side effects and 6.3% had side effects leading to death. Any-grade and grade 3 or higher treatment-emergent side effects affected 96.2% and 60.1% of patients, respectively, and any-grade and grade 3 or higher immune-mediated side effects occurred in 58.9% and 10.1%.

The most common treatment-emergent side effects included hypertension (57.6%), diarrhea (50%), hypothyroidism (41.1%), proteinuria (34.2%), fatigue (31%), palmar-plantar erythrodysesthesia syndrome (30.4%), dysphonia (29.1%) and diminished appetite (27.2%). Other treatment-emergent side effects included nausea (25.3%), decreased weight (22.8%), asthenia (22.2%), arthralgia (19.6%), stomatitis (19.6%), mucosal inflammation (15.2%) and pruritus (15.2%).

“Pembrolizumab plus lenvatinib for previously untreated advanced non–clear cell renal cell carcinoma: 3-year follow-up of the phase 2 KEYNOTE-B61 study,” by Dr. Laurence Albiges. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. Abstract 1.

Pembrolizumab plus lenvatinib for first-line advanced/​metastatic non-clear cell renal cell carcinoma (1L nccRCC) (MK-3475-B61) (KEYNOTE-B61). ClinicalTrials.gov. Updated February 17, 2025. Accessed July 21, 2025.

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

subscribe to CURE®’s newsletters here.

The phase 2 KEYNOTE-B61 trial demonstrated that combining Keytruda (pembrolizumab) with Lenvima (lenvatinib) as a first-line treatment for advanced non-clear cell kidney cancer significantly improved tumor shrinkage and survival rates. The trial reported an overall response rate of 50.6% and a disease control rate of 82.3%. The median progression-free survival was 17.9 months, and the median overall survival was 41.5 months. Despite promising results, the treatment was associated with high rates of side effects, including serious and treatment-discontinuing toxicities.

Data from the KEYNOTE-B61 trial show tumor shrinkage in different types of kidney cancer, including papillary and chromophobe subtypes. 

Clinical Trial Confirms Keytruda and Lenvima Benefit in Kidney Cancer 

Stereotactic body radiotherapy costs less and has shown better safety compared with immunotherapy and tyrosine kinase inhibitors in patients kidney cancer: © stock.adobe.com

Metastasis-directed radiotherapy alone showed encouraging results, including favorable survival rates and low side effects, for patients with oligometastatic clear cell renal cell carcinoma, a specific type of kidney cancer, according to a phase 2 trial presented at the 

With a median follow-up of 36.3 months, median progression-free survival was 34 months; median systemic therapy-free survival was 17.7 months; and 3-year overall survival was 86.5%.

Investigators noted that surveillance was associated with a median systemic therapy-free survival of 14.9 months in a phase 2 trial published in 

At baseline, 60% of patients (47 of 78) were minimal residual disease positive; among these, the median tumor fraction was 22.5 ppm. After 3 months, 25% of initially minimal residual disease-positive patients converted to negative.

Patients who were minimal residual disease negative showed improved systemic therapy-free survival compared with those who were positive since enrollment and since the 3-month assessment.

“Metastasis-directed therapy without systemic therapy offers advantages in costs, side effects, and clinic visits over frontline systemic therapies,” wrote study author Dr. Chad Tang, associate professor at the University of Texas MD Anderson Cancer Center, and coauthors. “[Metastasis-directed therapy] without systemic therapy showed favorable overall survival and side effect profiles. Biomarkers are needed at baseline to select patients and after therapy to guide surveillance versus systemic treatment. Circulating tumor DNA using a second-generation assay may help inform both roles.”

The trial enrolled patients with oligometastatic renal cell carcinoma with clear cell histology, up to five metastases, and no prior systemic therapy or more than one month off prior systemic therapy. Treatment included standard imaging and biopsy, blood draw, stereotactic radiation with or without local surgery to all disease sites, followed by imaging and blood draw. If progression occurred, the cycle restarted; otherwise, systemic therapy began.

Co-primary endpoints were progression-free survival per RECIST 1.1 and systemic therapy-free survival, defined as median systemic therapy-free survival greater than 25 months.

Immunotherapy alone or in combination and tyrosine kinase inhibitors cost approximately $150,000 to $300,000 annually, while stereotactic body radiation therapy costs about $15,000 to $40,000 per round; grade 3 or higher side effects occur in 45% to 85% and 5% to 10%, respectively; clinic visits occur at least monthly and one to two visits per radiation round.

Regarding safety, grade 2 or higher side effects were seen in 20.8% of patients, grade 3 or higher side effects in 6.7%, and grade 3 side effects in only one patient. Most common grade 2 side effects included musculoskeletal pain (10 patients), pneumonitis (five patients), cough (three patients), and shortness of breath (two patients). Most common grade 3 side effects were musculoskeletal pain (five patients), increased white blood cells (two patients), pleural effusion (one patient), and abdominal distension (one patient). The only grade 4 side effect was high blood sugar (one patient).

“Phase 2 trial of metastasis directed radiotherapy without systemic therapy (MRWS) for oligometastatic clear cell renal cell carcinoma (ccRCC) and investigation of circulating tumor DNA (ctDNA) as a personalized biomarker,” by Dr. Chad Tang. Presented at the 2025 Kidney Cancer Research Summit; July 17, 2025; Boston, MA.

“Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial,” by Dr. Brian I. Rini. 

A phase 2 trial demonstrated promising outcomes for metastasis-directed radiotherapy in oligometastatic clear cell renal cell carcinoma, showing favorable survival rates and minimal side effects. With a median follow-up of 36.3 months, the study reported a median progression-free survival of 34 months and a 3-year overall survival rate of 86.5%. The trial highlighted the potential of metastasis-directed therapy to reduce costs and side effects compared to systemic therapies. Biomarkers, particularly circulating tumor DNA, may guide patient selection and treatment strategies.

Stereotactic body radiotherapy costs less and has shown better safety compared with immunotherapy and tyrosine kinase inhibitors in patients kidney cancer. 

Ariana Pelosci

Venclexta And Azacitidine Fail to Improve MDS Survival

Welireg Plus Cabometyx Shows Tumor Control in Kidney Cancer Trial

Clinical Trial Confirms Keytruda and Lenvima Benefit in Kidney Cancer

Metastasis-Directed Radiotherapy Shows Improved Kidney Cancer Outcomes

Latest News