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Among patients with non–muscle-invasive bladder cancer, neoadjuvant mitomycin demonstrated favorable safety: © stock.adobe.com.

Among patients with non-muscle-invasive bladder cancer (NMIBC), neoadjuvant treatment with mitomycin C prior to transurethral resection of bladder tumor (TURBT) was associated with a favorable safety profile, trial results have shown.

Although an improvement in recurrence-free survival (RFS) compared with standard management was not observed at 12 months, an improvement in the 18-month RFS rate with mitomycin C could point to a potential delayed benefit with the neoadjuvant approach. These findings are from a phase 3, prospective, single-center, randomized trial (EudraCT 2021-003751-42) and were presented at the 2025 American Urological Association Annual Meeting.

Neoadjuvant: administered before the main treatment, such as surgery.

TURBT: a procedure to remove bladder tumors.

RFS: the time until the first recurrence of cancer.

ECOG performance status: a way of measuring patients’ ability to complete everyday tasks, with a lower score indicating greater independence. 

At a median follow-up of 19.4 months, findings showed that the estimated 12-months RFS rate was 88% in both the standard arm (27 patients) and the neoadjuvant mitomycin C arm (28 patients). The 18-month RFS rates were 71% in the standard arm versus 88% in the neoadjuvant mitomycin C arm.

“Even if statistical significance was not reached, the improvement in RFS at 18 months for the mitomycin Cgroup could suggest a potential delayed benefit of the neoadjuvant approach,” lead study author Dr. 

Roberto Contieri said in presentation of the data.

Contieri is a resident in urology at Humanitas University in Milan, Italy.

The randomized, open-label, single-center trial enrolled 63 patients with primary or recurrent NMIBC who had not received prior adjuvant intravesical therapy. Additional inclusion criteria required the presence of at least 1 tumor larger than 1 centimeter identified via imaging or cystoscopy; an ECOG performance status of less than 2; and a negative urine culture prior to enrollment.

Patients were randomly assigned to receive either neoadjuvant mitomycin C or no neoadjuvant therapy (control arm) prior to TURBT. In the experimental arm, patients underwent cystoscopy and tumor biopsy followed by mitomycin C instillation on day –14 and a second mitomycin C instillation on day –7. All patients underwent TURBT on day 0, followed by adjuvant intravesical therapy in accordance with European Association of Urology (EAU) guidelines. Follow-up cystoscopies were performed at three months and beyond.

The primary end point was RFS rate assessed at 12 and 18 months post-TURBT. Secondary end points included the safety profile of neoadjuvant mitomycin C and assessment of differences in histologic findings between pre-instillation biopsies and TURBT specimens. A sensitivity analysis was also conducted, including only patients who received adjuvant intravesical instillation with BCG or mitomycin C.

The baseline demographics and disease characteristics were well balanced between the neoadjuvant mitomycin C cohort (30 patients) and the control cohort (31 patients). Among patients in the neoadjuvant mitomycin C arm, all had a primary tumor at baseline compared with 94% in the control arm. According to the 2004/2022 World Health Organization (WHO) classification, 50% of patients in the neoadjuvant mitomycin C cohort had low-grade tumors, and 43% had high-grade tumors; 6.7% were classified as benign. In the control arm, 55% had low-grade tumors and 45% had high-grade tumors. Based on the 1973 WHO classification, the distribution of tumor grade was also comparable between groups, with 50% versus 52% classified as grade 1; 20% versus 10% as grade 2; and 33% versus 39% as grade 3 in the neoadjuvant mitomycin C and control arms, respectively.

Clinical T stage distribution indicated that the majority of patients in both groups had Ta disease (neoadjuvant mitomycin C arm, 80%; control arm, 74%). Carcinoma in situ (CIS) was present in 3.3% of patients in the neoadjuvant mitomycin C cohort and 10% in the control cohort. Presence of urothelial subtypes was observed in 6.7% versus 16% of patients, respectively. Rates of tumors larger than 3 centimeters were similar between groups (37% versus 35%), as were rates of multifocal tumors (30% versus 35%).

Most patients had negative surgical margins after TURBT; 87% of patients in both groups had no evidence of detrusor muscle invasion (DM negative). Re-TURBT was performed in 10% of patients receiving neoadjuvant mitomycin C and in 19% of those in the control group.

Within the neoadjuvant mitomycin C group, results of pre-mitomycin C biopsies showed that 67% of patients had low-grade disease, 20% had high-grade disease and 13% had specimens deemed non-evaluable. Histologic comparisons between biopsy and TURBT specimens demonstrated that tumor grade was confirmed in 67% of cases, with upgrading at TURBT occurring in 20% of patients. Additionally, visual evaluation of tumor response indicated that 7% of patients experienced tumor size reduction, and the majority (93%) had no visible change.

Findings showed neoadjuvant mitomycin C was generally well tolerated. Among patients who experienced treatment-related side effects (eight patients), all were grade 1 (mild) or 2 (moderate) in severity.

The most commonly reported side effect was hematuria, occurring in three patients (37.5%). Dysuria and itchy scalp were each reported in two patients (25%), and skin erythema was noted in one patient (12.5%).

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Articles

Neoadjuvant mitomycin C treatment in non-muscle-invasive bladder cancer (NMIBC) patients demonstrated a favorable safety profile, with mild to moderate side effects. Although no significant improvement in 12-month recurrence-free survival (RFS) was observed, an 18-month RFS rate improvement suggests potential delayed benefits. The phase 3 trial involved 63 patients, with balanced baseline demographics and disease characteristics. The primary endpoint was RFS at 12 and 18 months post-TURBT, while secondary endpoints included safety and histologic differences. The trial highlighted the potential of neoadjuvant mitomycin C in NMIBC management.

Among patients with non–muscle-invasive bladder cancer, neoadjuvant mitomycin demonstrated favorable safety.

Neoadjuvant Mitomycin C Shows Favorable Safety in Bladder Cancer

Subcutaneous Opdivo showed similar efficacy and safety to IV Opdivo in previously treated advanced or metastatic clear cell renal cell carcinoma.

Among patients with previously treated, advanced or metastatic clear cell renal cell carcinoma (ccRCC), subcutaneous Opdivo (nivolumab and hyaluronidase-nvhy, Opdivo Qvantig) was similarly effective, safe and tolerable when compared with intravenous (IV) Opdivo, clinical trial results have shown.

Updated results from the phase 3 CheckMate-67T clinical trial were presented during the 50

 Annual Oncology Nursing Society Congress.

Results showed that at a minimum follow-up of 15 months, the overall response rate (ORR) was 27% for subcutaneous Opdivo (248 patients) versus 21% for IV Opdivo (247 patients). ORR was a key secondary end point powered for noninferiority. Notably, the study previously met its co-primary end points of time-averaged serum concentration over the first 28 days and minimum serum concentration at steady state during the primary analysis.

Additional data from the updated analysis showed that the median progression-free survival (PFS) was 6.3 months with subcutaneous Opdivo versus 5.7 months with the IV formulation. The median time to response was 3.7 months in both arms. Six- and 12-month overall survival (OS) rates were 84% and 72%, respectively, for subcutaneous Opdivo, compared with 86% and 73%, respectively, for IV Opdivo.

"CheckMate-67T met its co-primary end points and key powered secondary end point at the primary analysis, demonstrating pharmacokinetic and efficacy noninferiority of subcutaneous [Opdivo] to IV [Opdivo], " lead study author Daniel Adamczyk of Bristol Myers Squibb and colleagues wrote in a poster presentation of the data. "These data further support the use of subcutaneous [Opdivo] as a new option with reduced administration time to improve patient treatment experience and health care efficiency."

In December 2024, the FDA approved subcutaneous Opdivo for use across approved adult solid tumor IV Opdivo indications as monotherapy, as monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy or in combination with chemotherapy or Cabometyx (cabozantinib). This regulatory decision was based on previously reported data from CheckMate-67T.

CheckMate-67T evaluated the safety and efficacy of subcutaneous Opdivo compared with the standard IV formulation in patients with previously treated advanced or metastatic ccRCC. Eligible patients had experienced disease progression during or after at least one prior systemic regimen and had not previously received immuno-oncology therapy.

Enrolled patients were randomly assigned to receive either subcutaneous Opdivo at 1200 milligrams co-formulated with recombinant human hyaluronidase PH20 at 20,000 units every four weeks or IV Opdivo at 3 milligrams per kilogram every two weeks. Patients continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, completion of two years of treatment, or death.

Beyond the co-primary pharmacokinetic end points and the key secondary end point of ORR, DOR, disease control rate, PFS and OS were other secondary end points assessed by blinded independent central review. Safety assessments included the incidence of side effects, treatment-related side effects, injection-site reactions and treatment discontinuations due to side effects or treatment-related side effects.

The study enrolled patients across 75 sites in 17 countries. Baseline characteristics and efficacy outcomes were evaluated in all randomized patients, while safety analyses included all patients who received at least one dose of Opdivo. Baseline patient demographics and disease characteristics were similar between the two arms.

Among patients treated with subcutaneous Opdivo (247 patients), any-grade side effects occurred in 93.1% of patients (grade 3, severe, or 4, life-threatening, 40.1%) compared with 94.3% (grade 3/4, 46.5%) for those given the IV formulation (245 patients). Treatment-related side effects of any grade were reported in 61.5% of patients in the subcutaneous arm, including 11.7% who experienced grade 3/4. Any-grade treatment-related side effects occurred in 65.7% of patients in the IV arm, including 17.1% who had grade 3/4.

Discontinuation due to any side effect occurred in 12.6% of patients in the subcutaneous arm, including 4.5% who discontinued treatment due to treatment-related side effects. These respective rates were 13.9% and 5.3% in the IV arm.

Immune-modulating medication was administered to 71.9% of patients who experienced an immune-mediated side effect in the IV arm (64 patients), and 32.8% of these patients received corticosteroids equivalent to at least 40 milligrams prednisone. These rates were 70.8% and 49.2%, respectively in the IV arm (65 patients).

Select any-grade treatment-related side effects in the subcutaneous Opdivo group included endocrine-related side effects at 12.6% (grade 3/4, 0.8%), gastrointestinal aide effects at 6.1% (1.2%), hepatic events at 9.3% (1.2%), pulmonary events at 4.9% (1.6%), renal events at 1.2% (0.4%), skin-related events at 24.3% (1.2%) and hypersensitivity or infusion reactions at 2.4% (0.4%).

In the IV group, any-grade treatment-related side effects included endocrine-related AEs at 18% (grade 3/4, 1.2%), gastrointestinal effects in 6.9% (0.4%), hepatic effects in 12.7% (1.2%), pulmonary effects in 3.3% (0.8%), renal effects in 2.4% (0.4%), skin-related effects in 27.3% (1.2%), and hypersensitivity or infusion reactions in 2.7% (0.4%).

Notably, treatment-related local injection site reactions (LISRs) were reported in 5% of patients in the subcutaneous arm versus 2% of patients in the IV arm. Five patients in the subcutaneous group needed intervention for LISRs, including four who received topical corticosteroids. All LISRs reported in the subcutaneous arm were grade 1, except for a single grade 2 occurrence.

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Subcutaneous Opdivo demonstrated comparable efficacy, safety, and tolerability to intravenous Opdivo in patients with advanced or metastatic clear cell renal cell carcinoma, as shown in the CheckMate-67T trial. The trial met its co-primary endpoints, confirming pharmacokinetic and efficacy noninferiority. Subcutaneous administration showed a slightly higher overall response rate and similar progression-free survival compared to intravenous administration. Safety profiles were comparable, with slightly fewer treatment-related side effects in the subcutaneous group. The FDA approved subcutaneous Opdivo for use in adult solid tumor indications based on these findings.

Subcutaneous Opdivo showed comparable effectiveness, safety and tolerability to IV Opdivo in advanced clear cell renal cell carcinoma.

Subcutaneous Opdivo Similarly Effective, Safe as IV for Advanced ccRCC

Bavencio plus best supportive care improves survival outcomes in advanced urothelial carcinoma, regardless of diabetes status.

Among patients with advanced urothelial carcinoma, first-line maintenance treatment with Bavencio (avelumab) plus best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC, regardless of diabetes mellitus status, according to exploratory analyses from the phase 3 JAVELIN Bladder 100 trial.

, which showed that in the subgroup of patients with diabetes mellitus, those who received Bavencio plus BSC (55 patients) achieved a median OS of 20.8 months versus 14.5 months with BSC alone. At two years, OS rates were 44.5% and 34.1%, respectively. At three years, OS rates were 33.1% and 20.3%, respectively. Among patients without diabetes, median OS was 24.7 months with Bavencio plus BSC versus 15.8 months with BSC alone. The two-year OS rates were 50.7% and 39.4%, respectively. The three-year OS rates were 36.6% and 31.9%.

Similarly, PFS was prolonged in both patient subgroups. In those with diabetes, median PFS was 5.6 months with Bavencio plus BSC versus 2 months with BSC alone. At two years, PFS rates were 18.5% and 9.2%, respectively. At three years, PFS rates were 13.5% and 5.5%, respectively. In patients without diabetes, median PFS was 5.4 months with Bavencio plus BSC versus 2.1 months with BSC alone. The 2-year PFS rates were 24.3% and 6.5%, respectively. The 3-year PFS rates were 16.3% and 5.3%, respectively.

Best supportive care (BSC): the optimal level of care provided to a patient.

Overall survival (OS): the average length of time that patients are alive after starting treatment or being diagnosed.

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

Lipase: an enzyme that helps digest fats in food.

Amylase: an enzyme that breaks down carbohydrates, like starches, into simple sugars.

“Overall, these results show that Bavencio frontline maintenance is associated with long-term efficacy benefits and consistent safety in patients with advanced urothelial carcinoma with or without diabetes mellitus who are progression free after first-line platinum-based chemotherapy,” explained lead study author Dr. Shilpa Gupta, director of Genitourinary Medical Oncology at the Cleveland Clinic Taussig Cancer Institute in Ohio.

Background and Design of the JAVELIN Bladder 100 Trial

The trial included patients with unresectable locally advanced or metastatic urothelial carcinoma who remained progression free following 4 to 6 cycles of first-line platinum-based chemotherapy. Patients were assigned to receive frontline maintenance with Bavencio plus BSC or BSC alone. The exploratory analysis assessed long-term efficacy and safety outcomes in subgroups of patients with or without documented diabetes mellitus at randomization.

At a data cutoff of June 4, 2021, with at least two years of follow-up, median OS was significantly prolonged in the Bavencio plus BSC cohort compared with BSC alone, at 23.8 months versus 15.0 months, respectively.Similarly, median PFS was 5.5 months in the Bavencio arm versus 2.1 months in the BSC alone arm, demonstrating the clinical benefit of Bavencio maintenance therapy in this setting.

Results also demonstrated the long-term safety of Bavencio maintenance therapy, with health-related quality of life preserved throughout treatment. These results contributed to the inclusion of Bavencio frontline maintenance in updated international guidelines as a recommended treatment option for patients with advanced urothelial carcinoma.

Additionally, the study explored the effects of diabetes mellitus, a known risk factor for bladder cancer that is more prevalent in older adults. Previous research has suggested that diabetes may be associated with reduced efficacy of immunotherapy in some cancers; however, data in urothelial carcinoma remain limited. As a result, this post hoc exploratory analysis from JAVELIN Bladder 100 was conducted to assess outcomes in subgroups of patients with or without diabetes mellitus at randomization.

Baseline Patient Characteristics of JAVELIN Bladder 100 Post Hoc Analysis

Baseline demographics and disease characteristics were assessed by diabetes mellitus status, and median follow-up was at least 38 months in both treatment arms.

The median age among patients with diabetes mellitus was 70 years (range, 51-86) in the Bavencio plus BSC arm and 72 years (range, 57-89) in the BSC alone arm. Among patients without diabetes mellitus, the median age was 68 years (range, 37-90) with Bavencio and 69 years (range, 32-85) with BSC alone. Most patients were male in both diabetes subgroups (87.3% and 91.5% with Bavencio and BSC alone in the diabetes cohort, respectively, and 73.9% and 75.9% in the non-diabetes cohort).

Most patients were enrolled from Europe. Smaller proportions were from North America, Asia, and Australasia.

In the diabetes subgroup, 52.7% of patients in the Bavencio arm and 32.2% in the BSC arm were PD-L1 positive. Among patients without diabetes, 54.2% and 51.5% were PD-L1 positive in the Bavencio and BSC arms, respectively.

In the Bavencio plus BSC arm, grade 3 or greater treatment-related side effects (TRSEs) were reported in 24.1% (13 patients) of patients with diabetes and 18.6% (54 patients) of those without diabetes. The most common grade 3 of higher TRSEs were increased lipase, amylase and anemia. In the BSC alone arm, 1.7% of patients in both subgroups experienced any-grade TRSEs.

Serious side effects (SEs) occurred in 37.0% of patients with diabetes and 29.3% of those without diabetes receiving Bavencio. Among these, 9.3% and 10.3%, respectively, were classified as serious TRSEs. In the BSC alone group, 23.7% of patients with diabetes and 20.3% of those without diabetes experienced serious SEs, and no serious TRSEs were reported.

Bavencio discontinuation due to TRSEs occurred in 11.1% of patients with diabetes and 14.8% of those without diabetes, with 9.3% and 12.1% of cases directly attributed to TRSEs. TRSEs leading to death were rare, occurring in 1.9% of patients with diabetes and 2.1% of those without diabetes in the Bavencio group.

Immune-related SEs (irSEs) were observed in 31.5% (17 patients) of patients with diabetes and 32.4% (94 patients) of those without diabetes treated with Bavencio, compared with 3.4% and 1.4% of patients in the BSC alone group.

The most commonly reported TRSEs of any grade in the Bavencio plus BSC arm included pruritus (11.1% versus 15.5% in the diabetes and non-diabetes cohorts, respectively), hypothyroidism (7.4% versus 11.7%), fatigue (5.6% versus 11.7%), and asthenia (9.3% versus 10.7%). Gastrointestinal-related TRSEs, including diarrhea (7.4% versus 11.0%) and nausea (9.3% versus 6.9%), were also frequently observed.

“Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): long-term outcomes from JAVELIN Bladder 100,” By Dr. Shipla Gupta, et al. 

“Avelumab first-line maintenance for advanced urothelial carcinoma: results from the JAVELIN Bladder 100 trial after ≥2 years of follow-up,” by Dr. Thomas Powles, et al. 

First-line maintenance treatment with avelumab (Bavencio) plus best supportive care (BSC) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with advanced urothelial carcinoma, regardless of diabetes mellitus status. The JAVELIN Bladder 100 trial demonstrated prolonged OS and PFS in both diabetic and non-diabetic subgroups, with consistent safety profiles. The study's findings have led to the inclusion of avelumab in international guidelines as a recommended treatment option. The trial also explored the impact of diabetes, a known risk factor for bladder cancer, on treatment efficacy.

Patients with advanced urothelial carcinoma had prolonged survival with Bavencio and BSC treatment, regardless of diabetes mellitus status.

Bavencio and BSC Extends Survival in Bladder Cancer, Regardless of Diabetes Status

Among patients with metastatic renal cell carcinoma (mRCC) who responded to frontline Bavencio (avelumab) and Inlyta (axitinib), updated phase 2 TIDE-A study findings presented at the 

 supported the feasibility of maintenance Bavencio with Inlyta treatment interruption.

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

Overall survival (OS): time from diagnosis or treatment start until death.

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

Partial responses (PR): reduction in tumor size, but not complete remission.

Disease control rate: percentage of patients with stable, partial, or complete response.

Hepatic metastases: cancer spread to the liver.

ECOG performance status of 0 or 1: scale of daily activity ability (0 = fully active, 1 = some limitations).

Bulky or symptomatic disease: large cancer-causing noticeable symptoms.

Findings showed that at a median follow-up of 31.7 months, patients in the overall population (75 patients) achieved a median progression-free survival (PFS) of 27.9 months. The median overall survival (OS) was not reached (NR), and the 24-month OS rate was 85%.

Among the patients who interrupted Inlyta at week 36 (29 patients), the median PFS and OS were both NR; the 24-month PFS and OS rates were 58% and 82%, respectively. The median duration of first Bavencio maintenance was 16 weeks.

“This analysis with a longer follow-up confirmed the feasibility of [Vascular endothelial growth factor, VEGF, tyrosine kinase inhibitors, TKI] interruption and the high response rate after VEGFR TKI reintroduction in patients receiving [Bavencio] maintenance,” lead study author Dr. Daniela Arduini, of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, and colleagues wrote in a poster presentation of the data.

Following Inlyta interruption, five patients remained on Bavencio monotherapy without disease progression. One patient discontinued Bavencio due to side effects after 35.8 months of maintenance. Two patients continued Bavencio despite evidence of disease progression, and 21 patients restarted Inlyta.

Among patients who restarted Inlyta, the objective response rate (ORR) was 50%, with partial responses (PR) in 10 patients, stable disease in eight patients and progressive disease in two. The median PFS following Inlyta reintroduction was 17.2 months.

“The progression during maintenance with [Bavencio] alone did not affect the response to the subsequent TKI reintroduction. This strategy warrants further investigation in a randomized trial,” study authors added.

TIDE-A enrolled patients with metastatic RCC who had measurable disease, an ECOG performance status of 0 or 1, no bulky or symptomatic disease and no hepatic metastases.

Patients were excluded if they received prior systemic therapy for advanced RCC; received prior adjuvant or neoadjuvant treatment; had an active seizure disorder or evidence of active brain metastases, spinal cord compression, or carcinomatous meningitis; or had a history of another malignancy within two years prior to enrollment, with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ.

All enrolled patients initially received combination therapy with Bavencio at 800 milligrams (mg) once every two weeks plus Inlyta at 5 mg twice per day for 36 weeks. At week 36, patients underwent tumor evaluation, and those who achieved a PR — defined as a tumor volume reduction of at least 30% from baseline — discontinued Inlyta and continued Bavencio monotherapy at 800 mg once every two weeks until disease progression.

If disease progression occurred during Bavencio maintenance — defined as a tumor volume increase of at least 20% from the week 36 assessment — Inlyta was reintroduced at the same dose and discontinued again upon patients achieving a new PR. Patients who had stable disease at week 36 continued combination therapy until disease progression. Those with progressive disease at week 36 stopped all treatment.

The trial’s primary end goal was ORR at eight weeks following Inlyta discontinuation and initiation of Bavencio maintenance after 36 weeks of combination therapy. Secondary end goals included PFS, ORR for the combination period, disease control rate, OS, safety and patient-reported outcomes.

“Updated results of the TIDE-A study evaluating avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (mRCC),” by Dr. Arduini D, et al., 

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Updated findings from the TIDE-A study indicate the feasibility of maintenance Bavencio with Inlyta interruption in metastatic renal cell carcinoma (mRCC) patients. At a median follow-up of 31.7 months, the overall population achieved a median progression-free survival (PFS) of 27.9 months, with a 24-month overall survival (OS) rate of 85%. Among patients who interrupted Inlyta, the median PFS and OS were not reached, with 24-month rates of 58% and 82%, respectively. The study supports further investigation of this strategy in a randomized trial.

Updated TIDE-A study findings show that maintenance Bavencio with Inlyta treatment interruption is feasible in patients with metastatic renal cell carcinoma.

Jax DiEugenio

Neoadjuvant Mitomycin C Shows Favorable Safety in Bladder Cancer

Subcutaneous Opdivo Similarly Effective, Safe as IV for Advanced ccRCC

Bavencio and BSC Extends Survival in Bladder Cancer, Regardless of Diabetes Status

Bavencio Maintenance After Inlyta Interruption Shows Feasibility in mRCC

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