Roman Fabbricatore

Columvi combo enhances survival outcomes vs Rituxan combo in R/R DLBCL: © stock.adobe.com.

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), Columvi (glofitamab) plus chemotherapy with gemcitabine and oxaliplatin (GemOx) demonstrated enhanced survival outcomes compared with Rituxan (rituximab) plus GemOx, according to a two-year follow-up data from the phase 3 STARGLO trial presented at the 

Efficacy data from the trial revealed that after a median follow-up of 24.7 months, Columvi plus GemOx exhibited superior overall survival versus Rituxan/GemOx; the median overall survival was not evaluable versus 13.5 months. Additionally, the 24-month overall survival rate in each arm was 54.4% versus 33.6%. The median progression-free survival in each arm was 13.8 months versus 3.6 months, with respective 18-month progression-free survival rates of 46.5% versus 23.0%.

The objective response rates in the Columvi and Rituxan arms were 68.3% versus 40.7%. Furthermore, the complete response rate with Columvi was 58.5% versus 25.3% with Rituxan. Among responders to Columvi, the median duration of complete response was not reached versus 24.2 months for responders to Rituxan. A total of 42.1% of the Columvi arm and 17.6% of the Rituxan arm had an ongoing complete response at data cut-off.

Following the end of treatment, the median overall survival and progression-free survival was not estimable in the Columvi arm. The respective 12-month overall survival and progression-free survival rates were 89.3% and 82.4%.

“With 2-year follow-up data of the [phase 3] STARGLO trial, Columvi/GemOx continues to show a sustained benefit in overall survival, progression-free survival, and response compared to [Rituxan]/GemOx,” Dr. Jeremy S. Abramson, director of the Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital and a professor of Medicine at Harvard Medical School, said in the presentation. “We saw that more than half of patients remain alive after Columvi/GemOx, and the majority of responders were not only alive, but progression-free.”

Patients in the phase 3 trial were randomly assigned to receive Columvi plus GemOx (183 patients) or Rituxan plus GemOx (91 patients). Those in the Columvi arm received step-up dosing in cycle one, then a 30 milligram (mg) target dose every 31 days starting cycle two, day one. Patients were given eight cycles of Columvi with GemOx followed by four cycles of Columvi as monotherapy.

In the Rituxan and Columvi arms, respectively, the median age was 69.0 years (range, 20-84) versus 68.0 years (range, 22-88), 58.2% versus 57.4% of patients were male, and 56.0% versus 47.0% were Asian. A total of 62.6% versus 62.8% had one prior line of therapy, 51.6% versus 57.9% were primary refractory to last treatment, and 90.9% versus 88.9% had an ECOG performance status of zero or one. Furthermore, 77.8% versus 66.7% had Ann Arbor stage 3 or 4 disease, 15.6% versus 12.6% had bulky disease of 10 centimeter or greater, and 8.8% versus 7.7% received prior CAR-T cell therapy.

The primary end point of the trial was overall survival. Secondary end points included independent review committee–assessed progression-free survival and complete response rates, with a landmark analysis of patients with complete responses at end of treatment performed.

Among those treated with Rituxan and Columvi, 17.0% versus 52.3% experienced serious side effects. Furthermore, 40.9% versus 76.7% experienced grade 3 (serious) or higher side effects, including 4.5% versus 7.0% of patients on each respective arm dying. Side effects leading to treatment discontinuation occurred in 12.5% and 25.6% of the Rituxan and Columvi arms.

In the Columvi arm, the incidence of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was 44.8% and 2.3%, with respective grade 3/4 rates of 2.3% and 0.6%. Infections of any grade occurred in 29.5% and 55.2% of the Rituxan and Columvi arms, respectively, with 9.1% and 16.9% of patients experiencing grade 3 (serious)/4 (life-threatening) infections, and 3.4% versus 3.5% dying from infections.

Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO. 

 2025;43(suppl 16):7015. doi:10.1200/JCO.2025.43.16_suppl.7015

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Articles

Columvi plus chemo had enhanced survival outcomes vs Rituxan plus chemo in patients with relapsed/refractory diffuse large B-cell lymphoma. 

Columvi Combo Enhances Survival Outcomes in R/R Lymphoma Subgroup 

Neoadjuvant chemotherapy plus chemoradiation was safe and effective for long-term bladder preservation in select patients with muscle-invasive bladder cancer.

Among patients with nonmetastatic, muscle-invasive bladder cancer (MIBC), treatment with neoadjuvant cisplatin-based combination chemotherapy (NAC) plus bladder-saving concurrent chemoradiation therapy was effective and safe in the long term, according to findings presented at the 2025 ASCO Genitourinary Cancers Symposium.

Efficacy data revealed that after a median follow-up of 96 months, the median disease-free survival (DFS) in patients treated with NAC followed by CRT for nonmetastatic MIBC was 56.6 months, with a five-year DFS rate of 49.2%. Furthermore, the median bladder intact DFS (BI-DFS) in this patient group was 45.6 months, and the five-year BI-DFS was 47.6%. Additionally, the median overall survival (OS) was 105 months with a five-year OS rate of 62.2%.

“[Neoadjuvant, cisplatin-based chemotherapy plus] concurrent chemoradiotherapy is a safe and effective bladder-sparing approach with encouraging long-term outcomes in carefully selected patients with MIBC,” Dr. Meghan E. Mahoney of the Division of Medical Oncology at the Tom Baker Cancer Centre in Calgary, Alberta, Canada, wrote in the presentation with study coinvestigators.

The study investigators contextualized the study background by highlighting a paucity of long-term data on the efficacy and tolerability of trimodality therapy in patients with MIBC opting for bladder-sparing approaches.

Neoadjuvant: administered prior to the primary treatment, such as surgery.

Disease-free survival: the time after treatment that a patient lives without signs or symptoms of cancer.

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

Maximal transurethral resection of a bladder tumor: the removal of a tumor through the urethra.

Cystoscopy: a procedure to examine the bladder and urethra.

Radical cystectomy: surgical removal of the bladder.

ECOG performance status: a way to measure patients’ ability to complete daily tasks, with a lower number indicating greater independence.

Hydronephrosis: when the kidney becomes swollen due to a buildup of urine.

A total of 56 patients with nonmetastatic MIBC who were given NAC followed by bladder-sparing CRT between 2008 and 2017 at the Princess Margaret and Durham Regional Cancer Centers were included in the retrospective chart review. The primary outcomes were five-year DFS, BI-DFS and OS.

Patients initially underwent maximal transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant treatment with gemcitabine plus cisplatin for two to four cycles. Following the second cycle of neoadjuvant treatment, imaging occurred in all patients, and those experiencing disease progression underwent cystoscopy before undergoing immediate radical cystectomy plus lymph node dissection. Furthermore, following the fourth cycle, all patients underwent imaging and cystoscopy, and those who experienced disease progression underwent maximal re-TURBT before undergoing immediate radical cystectomy plus lymph node dissection.

Responders to neoadjuvant treatment and those with stable disease were treated with external beam radiation therapy (EBRT) at a dose of 60 to 66 Gy to the bladder and pelvic lymph nodes, as well as concurrent weekly cisplatin at 40 mg/m

 for six weeks. Surveillance cystoscopy, imaging and urine cytology occurred after CRT every three to four months.

During the surveillance period, those with no recurrence continued surveillance. Additionally, those with non-MIBC recurrence repeated TURBT with or without Bacillus Calmette-Guerin treatment. Those with MIBC recurrence underwent salvage cystectomy. Furthermore, patients who experienced distant recurrence during the surveillance period were treated with systemic therapy.

Patients included in the analysis had a median age of 72 years and 79% were male. Additionally, 55% of patients had formerly smoked, with 20% of patients identifying as current smoking. Patients primarily had an ECOG performance status of 0 (66%) or 1 (32%). The median creatinine clearance was 59 mL/min, the median tumor size was 4.1 cm and 25% of patients had hydronephrosis.

Patients had clinical stage 2 (59%), 3 (34%), or 4 (7%) disease, and the most common histologies were pure urothelial carcinoma (UC; 63%), squamous UC (23%) and plasmacytoid variant UC (13%). A total of 30% and 18% of patients had carcinoma-in-situ and lymphovascular invasion, respectively. Overall, 41% of patients experienced disease recurrence, with 20% of patients experiencing local recurrence, 14% experiencing recurrence requiring cystectomy and 21% experiencing distant recurrence.

The primary NAC regimens were gemcitabine/cisplatin every 21 days (34%) or split gemcitabine/cisplatin every 21 days (57%). Overall, 5%, 32% and 63% of patients underwent two, three and four NAC cycles, with 95% of patients completing planned NAC treatment. The most common grade 3 (severe) or 4 (life-threatening) NAC-related toxicities included neutropenia (11%), thrombocytopenia (4%), infection (4%) and anemia (2%). NAC dose reductions occurred in 55% of patients with a median dose reduction percentage of 25%, and 39% of patients experienced NAC dose delays.

Additionally, the reasons for administering trimodality therapy included patient preference (59%), comorbidities related to radical cystectomy (36%) or some combination of both factors (4%). Most patients had a planned radiation therapy dose of 60 Gy or greater (91%), and all patients completed planned radiation. Furthermore, 86% of patients completed 60% or more of planned concurrent cisplatin dosing.

“Long-term outcomes of neoadjuvant chemotherapy (NAC) before bladder-sparing chemoradiotherapy (CRT) for patients with nonmetastatic, muscle-invasive bladder cancer (MIBC),” by Dr. Meghan E. Mahoney, et al., 

Neoadjuvant cisplatin-based chemotherapy combined with bladder-sparing concurrent chemoradiation therapy demonstrates long-term efficacy and safety in nonmetastatic muscle-invasive bladder cancer (MIBC). After a median follow-up of 96 months, the median disease-free survival (DFS) was 56.6 months, with a five-year DFS rate of 49.2%. The median bladder intact DFS was 45.6 months, and the five-year rate was 47.6%. Overall survival (OS) reached a median of 105 months, with a five-year OS rate of 62.2%. Trimodality therapy was chosen due to patient preference and comorbidities.

For some patients with bladder cancer, neoadjuvant chemotherapy plus bladder-saving concurrent chemoradiation therapy was effective in the long term.

Neoadjuvant Chemotherapy Plus Chemoradiation Safe, Effective in Bladder Cancer

Patients with intermediate-risk prostate cancer had a 15-year prostate cancer–specific survival rate of 91% with EBRT, with or without short-term ADT: © Beaunitta Van Wyk/peopleimages.com - stock.adobe.com

For patients with intermediate-risk prostate cancer (IRPC), external beam radiation therapy (EBRT) with or without short-term neoadjuvant androgen deprivation therapy (STAD) elicited 15-year survival, according to a study presented in a poster session at the 

Cancer-specific survival (PCSS): percentage of patients not dead from cancer.

External beam radiation therapy (EBRT): radiation treatment targeting tumors.

Short-term neoadjuvant androgen deprivation therapy (STAD): temporary hormone therapy before treatment.

Freedom from biochemical failure (FFBF): no PSA increase after treatment.

Overall survival (OS): percentage of patients alive over time.

Prostate-specific antigen (PSA): protein used to monitor prostate cancer.

Gleason group: system grading prostate cancer aggressiveness. 

Data from the trial revealed that at a median follow-up of 12 years and a maximum of 19.8 years, the 15-year prostate cancer–specific survival (PCSS) rate was 91% for patients with IRPC undergoing STAD plus EBRT and those receiving EBRT alone. Additionally, the 15-year overall survival (OS) rate was 53% for those undergoing STAD plus EBRT and 51% for those undergoing EBRT alone.

Additionally, the metastasis-free survival (MFS) rate after 15 years was 85% versus 83% in the STAD/EBRT and EBRT arms, respectively. Furthermore, the 15-year freedom from biochemical failure (FFBF) rates were 52% and 49% in each respective arm.

“After 15 years of follow-up, [patients with] IRPC treated with STAD [for six months with or without] EBRT [at] 73.8 Gy experienced a PCSS [rate] of 91%, despite a high prostate-specific antigen [PSA] failure rate of 49% to 52%,” Dr. Barry W. Goy, radiation oncologist at Kaiser Permanente Los Angeles Medical Center, wrote in the poster. “It is unclear if six months of STAD in addition to EBRT can improve PCSS or OS for IRPC, or just merely delay PSA progression.”

Patients with IRPC (566 patients) were enrolled and treated from 2004 to 2007 with EBRT at a median dose of 7380/180cGY to the 98% prostate isodose. Of those patients, 336 were given leuprolide for a median duration of six months, and the remaining 230 were treated with EBRT alone. FFBF was defined by a PSA nadir greater than 2 ng/ml.

Additional data from the study showed that the 10-year PCSS rate was 96% in patients who underwent STAD plus EBRT versus 98% in those who underwent EBRT alone at a dose of 73.8 Gy after a median follow-up of 12 years. Comparatively, a previous study published in 

, which enrolled 206 patients with localized, unfavorable-risk prostate cancer, showed an approximately 94% 10-year PCSS rate with STAD plus EBRT versus approximately 81% with EBRT alone. Patients on trial received 70 Gy of EBRT for a median follow-up of 7.6 years.

Furthermore, in a separate trial published in the 

, which enrolled and assigned 1979 patients with stage T1b, T1c, T2a and T2b prostate adenocarcinoma and a PSA level of 20 ng/ml to receive either EBRT alone (992 patients) or EBRT with STAD for four months (987 patients). At an EBRT dose of 66.6 Gy and a median follow-up of 9.1 years, the 10-year PCSS rates were approximately 97% in the EBRT plus STAD arm and approximately 89% in the EBRT alone arm.

Multivariate analysis revealed that side effects were greater in the STAD group than those who underwent EBRT alone. Notable clinical factors included clinical stage, inactive PSA and Gleason group.

Additionally, a previous study presented by Goy at the 2018 ASCO Genitourinary Cancer Symposium showed that of 574 patients who underwent EBRT at a median dose of 75.3 Gy, the 10-year FFBF rate was 58.8%. This matched the 10-year FFBF rate for those undergoing radical prostatectomy (819 patients) and was numerically lower than those undergoing brachytherapy (110 patients).

“Fifteen-year outcomes of external radiation with or without six months of neoadjuvant deprivation therapy for intermediate risk prostate cancer,” By Dr. Goy BW, et al. 

“Androgen suppression and radiation versus radiation alone for prostate cancer: a randomized trial,” By Dr. D’Amico AV, et al. 

“Radiotherapy and short-term androgen deprivation for localized prostate cancer,” By Dr. Jones CU, et al. 

“Ten year treatment outcomes of radical prostatectomy versus external beam radiation therapy versus. brachytherapy for 1,503 patients with intermediate risk prostate cancer,” By Dr. Goy BW, et al. 

A study presented at the 2025 ASCO Genitourinary Cancer Symposium evaluated the 15-year outcomes of external beam radiation therapy (EBRT) with or without short-term neoadjuvant androgen deprivation therapy (STAD) in patients with intermediate-risk prostate cancer (IRPC). The findings indicated similar prostate cancer-specific survival (PCSS) and overall survival (OS) rates between the two treatment groups. However, the study highlighted a high prostate-specific antigen (PSA) failure rate. Multivariate analysis showed increased side effects in the STAD group. The study's results were compared with previous trials, revealing varying outcomes based on treatment modalities and follow-up durations.

Patients with intermediate-risk prostate cancer had a 15-year prostate cancer–specific survival rate of 91% with EBRT, with or without short-term ADT.

EBRT Regimens Show Long-Term Survival Outcomes in Prostate Cancer

Among patients with clear cell renal cell carcinoma, improved responses were observed with Lenvima plus Welireg versus Keytruda plus Lenvima. © unlimit3d - stock.adobe.com

Treatment with Lenvima (lenvatinib) in combination with Welireg (belzutifan) exhibited durable antitumor activity and a safety profile consistent with prior reports of each individual agent in patients with histologically confirmed locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) whose disease progressed on or following PD-L1 inhibitor or VEGF-tyrosine kinase inhibitor treatment, according to cohort analysis findings from the phase 1/2 KEYMAKER-U03 substudy 03B presented at the 

2025 ASCO Genitourinary Cancers Symposium.

Progression-free survival (PFS): the amount of time a patient lives with a disease without it worsening.

Overall survival (OS): the amount of time a patient survives after being diagnosed with or starting treatment for a disease.

Clinical benefit rate (CBR): represents the percentage of patients who experience a positive clinical benefit from a treatment.

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

Efficacy data revealed that between three arms — Keytruda (pembrolizumab)/Welireg (62 patients; arm B4), Lenvima/Welireg (64 patients; arm B5) and Keytruda/Lenvima (73 patients; reference arm) –– Lenvima/Welireg elicited the greatest number of responses. The objective response rate (ORR) in arms B4, B5, and the reference arm, respectively, were 19.4%, 46.9% and 39.7%. In each respective arm, two, one and zero patients attained complete responses and 10, 29 and 29 attained partial responses.

Further data exhibited a clinical benefit rate (CBR) of 32% in arm B4, 59% in arm B5 and 58% in the reference arm. In the respective arms, the median duration of response (DOR) was not reached, 22.1 months and 8.3 months.

In arm B4, arm B5, and the reference arm, the median progression-free survival (PFS) was 5.4 months, 12.5 months and 9.4 months, respectively. The six-month PFS rates in the respective arms were 41.8%, 63.1% and 66.7%, and the 12-month rates were 28.6%, 51.8% and 34.5%.

The median overall survival (OS) was 27.4 months in arm B4, 32.3 months in arm B5 and not reached in the reference arm. The 12-month OS rates were 67.9%, 79.5% and 81.7% in the respective arms, with 18-month rates of 57.6%, 74.4% and 73.2%.

In arm B4, 66.1% of evaluable patients experienced a target lesion size reduction, 28.8% of whom had a reduction of 30% or greater. In arm B5, it was 88.3% and 60.0%, respectively, as well as 91.8% and 49.3% in the reference arm.

“In KEYMAKER-U03 Substudy 03B, in a patient population with many prior treatment lines, we see that Lenvima plus Welireg showed an ORR of [46.9%] with a median PFS of 12.5 months,” Dr. Katy Beckermann, medical oncologist and medical director of Genitourinary Clinical Research at Tennessee Oncology, stated in the presentation. “We saw results from the Keytruda plus Welireg arm were similar to those observed in the Welireg monotherapy arm in the phase 3 LITESPARK-005 study. ... Results from Substudy 03B showed promising clinical activity in the Lenvima plus Welireg arm, and we recognized that the phase 3 LITESPARK-011 trial was ongoing and was testing this combination compared [with] Cabometyx [cabozantinib].”

In the LITESPARK-005 study, patients with advanced ccRCC who received previous immune checkpoint and antiangiogenic therapies were randomly assigned to receive either 120 mg of oral Welireg or 10 mg of oral Afinitor (everolimus) until disease progression or unacceptable toxicity. At the first interim analysis, the median PFS in the Welireg arm was 5.6 months, with an 18-month PFS rate of 24%. Additionally, the confirmed ORR was 21.9%, and at a second interim analysis, the median OS was 21.4 months with an 18-month OS rate of 55.2%.

The LITESPARK-011 trial is currently ongoing and randomly assigning patients with advanced RCC who experienced progression after prior anti–PD-L1 therapy to receive either Welireg/Lenvima or Cabometyx (cabozantinib). The primary study end points are PFS and OS.

Patients enrolled in KEYMAKER-U03 substudy 03B were randomly assigned to receive Keytruda/Welireg or Lenvima/Welireg. Arms B4 (10 patients) and B5 (12 patients) had a safety lead-in phase wherein approximately 10 patients were enrolled before random assignment. Afterwards, patients were assigned to arm B4 (52 patients), arm B5 (52 patients) or the reference arm (73 patients) during the efficacy phase.

Patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk factors and prior treatment with CTLA-4 inhibition. Additionally, patients were required to have measurable disease criteria by blinded independent review committee (BICR) and a Karnofsky performance status score of 70% or greater for enrollment.

Those in arm B4 were treated with 400 mg of intravenous Keytruda every six weeks plus 120 mg of daily oral Welireg. Patients in arm B5 were treated with 20 mg of daily oral lenvatinib plus 120 mg of daily oral Welireg. Patients in the reference arm were treated with 400 mg of intravenous Keytruda every six weeks plus 20 mg of daily oral lenvatinib.

Across all cohorts, 100% of patients experienced any-grade side events. In arms B4, B5 and the reference arm, grade 3 (severe) to 5 (fatal) side effects occurred in 64.5%, 77.8% and 76.7% of the respective arms. Side effects leading to dose interruption occurred in 54.8%, 71.4%, and 58.9% of each respective arm, with side effect-related discontinuations occurring in 16.1%, 14.3% and 16.4%, and side effect-related deaths occurring in 3.2%, 4.8% and 2.7% of patients.

Treatment-related side effects occurred in 95.2%, 95.2% and 98.6% of the respective arms. Grade 3 to 5 treatment-related side effects occurred in 41.9%, 60.3% and 49.3%, respectively, with treatment-related side effects leading to treatment continuation occurring in 11.3%, 9.5% and 12.3% of the respective arms. Treatment-related side effects resulting in death occurred in 0%, 3.2% and 1.4%, respectively.

The most common treatment-related side effects in the respective arms included anemia (69.4%, 65.1%, 4.1%), diarrhea (4.8%, 42.9%, 56.2%), hypertension (0%, 36.5%, 52.1%), fatigue (24.2%, 46.0%, 34.2%) and nausea (12.9%, 38.1%, 24.7%).

:“KEYMAKER-U03 Substudy 03B: pembrolizumab (pembro) and targeted therapy combinations for advanced clear cell renal cell carcinoma (ccRCC).” By Dr Laurence Albiges. 

The combination of Lenvima (lenvatinib) and Welireg (belzutifan) demonstrated significant antitumor activity and a consistent safety profile in patients with advanced clear cell renal cell carcinoma (ccRCC) who had progressed after PD-L1 or VEGF-tyrosine kinase inhibitor treatments. The Lenvima/Welireg arm showed the highest objective response rate (ORR) and clinical benefit rate (CBR) compared to other treatment arms. The study highlighted the promising efficacy of this combination, with ongoing trials comparing it to Cabometyx (cabozantinib) to further evaluate its potential in ccRCC treatment.

Among patients with clear cell renal cell carcinoma, improved responses were observed with Lenvima plus Welireg versus Keytruda plus Lenvima.

Roman Fabbricatore

Columvi Combo Enhances Survival Outcomes in R/R Lymphoma Subgroup

Neoadjuvant Chemotherapy Plus Chemoradiation Safe, Effective in Bladder Cancer

EBRT Regimens Show Long-Term Survival Outcomes in Prostate Cancer

Antitumor Activity Elicited in ccRCC Following Lenvima/Welireg Treatment

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