Gina Mauro

Data presented at the 2021 American Urological Association Annual Meeting showed that adjuvant pembrolizumab (Keytruda) improved disease-free survival (DFS) vs placebo across all prespecified subgroups, including region, type of nephrectomy, sarcomatoid features, disease risk category, tumor grade, and PD-L1 status.

The benefit was most significantly pronounced in patients who underwent partial nephrectomy (HR, 0.22; 95% CI, 0.05-1.04) and those who had M1 no evidence of disease (NED; HR, 0.29; 95% CI, 0.12-0.69). The data were derived from the phase 3 KEYNOTE-564 trial (NCT03142334).

“Although numbers of participants with certain disease risk features were small, the DFS benefit was consistent across subgroups,” lead study author Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center, and senior physician at Dana-Farber Cancer Institute, as well as Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, said in a virtual presentation during the meeting. “Safety results were in line with expectations and no new safety signals were observed.”

Earlier findings from the KEYNOTE-564 study were 

presented during the 2021 ASCO Annual Meeting

 to a new supplemental biologics license application for adjuvant pembrolizumab as a treatment for patients with RCC who are at intermediate-high or high risk of recurrence after nephrectomy or following nephrectomy and resection of metastatic lesions.

 The agency is expected to decide on the application by December 10, 2021.

In the double-blind, multicenter, phase 3 KEYNOTE-564 study, investigators explored pembrolizumab vs placebo following nephrectomy in patients with clear cell RCC. Specifically, patients’ disease had to meet criteria that categorized them as intermediate-high risk for recurrence, which included: pT2, grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0; high-risk pT4, any grade, N0, M0; any pT, any grade, N-positive, M0; or M1 with NED after surgery.

Stratification factors included metastatic status (M0 vs M1 NED), as well as ECOG performance status (0 vs 1) and region (US vs non-US), both in the M0 group only.

To be eligible for enrollment, patients must have undergone nephrectomy within 12 weeks prior to randomization, could not have previously received systemic therapy, had to have an ECOG performance status of 0 or 1, and a tissue sample must have been obtainable for PD-L1 testing.

All patients underwent 1:1 randomization to receive pembrolizumab at 200 mg every 3 weeks or placebo every 3 weeks, both for approximately 1 year.

The primary end point of the trial was investigator-assessed DFS; secondary end points were overall survival (OS) and safety.

The first prespecified interim analysis was planned following approximately 265 DFS events and a 12-month minimum follow-up. Following a minimum 15-month follow-up, 260 DFS events had occurred, and 51 OS events occurred. DFS and OS were estimated via Kaplan-Meier.

The median age of study participants was 60 years (range, 25-84), 71% of patients were male, and 73.5% had an ECOG performance status of 1. Moreover, 25.95% of patients were from North America, 37.7% were from the European Union, and 37.3% were from the rest of world. Most patients (92.4%) underwent radical nephrectomy and 83.7% had absent sarcomatoid features.

The majority of patients (86.5%) had M0 intermediate-high risk disease, 7.6% had M0 high-risk disease, and 5.8% had M1 NED. Moreover, 88.6% of patients had a primary tumor stage of T3; 3.5%, 30.4%, 43.5%, 22.3% of patients had tumor grade 1, 2, 3, and 4, respectively. Additionally, 93.8% of patients had N0 disease. Seventy-five percent of patients had a PD-L1 combined positive score of at least 1.

The data cutoff date was December 14, 2020. At a median follow-up of 24.1 months (range, 14.9-41.5), the median DFS in the intent-to-treat population was not reached with either pembrolizumab (n = 496) or placebo (n = 498) per investigator assessment (HR, 0.68, 95% CI, 0.53-0.87; 

 = .0010). The estimated 1-year DFS rates were 85.7% and 76.2% with pembrolizumab and placebo, respectively; the 2-year rates were 77.3% and 68.1%, respectively.

When examined across subgroups, additional factors that were associated with a more significant DFS benefit with pembrolizumab was patients of the European Union (HR, 0.49; 95% CI, 0.32-0.74), present sarcomatoid features (HR, 0.56; 95% CI, 0.29-1.06), and grade 4 tumors (HR, 0.57; 95% CI, 0.37-0.87).

OS data remain immature and the median OS has not yet been reached in either arm. However, there is a trend toward improved survival with pembrolizumab (HR, 0.54; 95% CI, 0.30-0.96; 

 = .0164). Eighteen events (3.6%) have occurred in the pembrolizumab arm compared with 33 events (6.6%) in the placebo arm. The 1-year DFS rates were similar at 98.6% and 98.0% with pembrolizumab and placebo, respectively; at 2 years, these rates were 96.6% and 93.5%, respectively.

Safety findings showed that all-cause adverse events (AEs) occurred in 96.3% of patients on pembrolizumab and 91.1% of those on placebo; grade 3 to 5 AEs occurred in 32.4% and 17.7% of patients, respectively, and 20.7% and 2.0% of patients, respectively, had AEs led that led to treatment discontinuation. Two patients on pembrolizumab had AEs that led to death compared with 1 patient on placebo.

Serious all-cause AEs occurred in 20.5% of patients on pembrolizumab and 11.3% of patients on placebo; these AEs led to treatment discontinuation in 10.0% and 1% of patients, respectively. Treatment-related AEs (TRAEs) that were all-grade and grades 3 to 5 occurred in 79.1% and 18.9% of pembrolizumab-treated patients and 53.4% and 1.2% of placebo-treated patients, respectively. A total 17.6% of patients on pembrolizumab had AEs led to treatment discontinuation vs 0.6% on placebo. No TRAEs on either arm led to death.

Grade 3/4 AEs that occurred in more than 5% of patients on pembrolizumab were fatigue, diarrhea, rash, pruritis, hypothyroidism, hyperthyroidism, arthralgia, myalgia, and asthenia. A total 7.4% of patients on pembrolizumab received high-dose (≥40 mg/day) of systemic corticosteroids for immune-mediated AEs compared with 0.6% of those on placebo.

1. Choueiri T, Pembrolizumab (pembro) vs placebo as post nephrectomy adjuvant therapy for patients (pts) with renal cell carcinoma (RCC): randomized, double-blind, phase 3 KEYNOTE-564 study. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Plenary session. https://bit.ly/392XAL7

2. FDA grants priority review to Merck’s supplemental biologics license application for KEYTRUDA (pembrolizumab) as adjuvant therapy in certain patients with renal cell carcinoma (RCC) following surgery. News release. Merck. August 10, 2021. Accessed September 14, 2021. https://bit.ly/3jEcyMt

Articles

“Although numbers of participants with certain disease risk features were small, the DFS benefit was consistent across subgroups,” said lead study author Toni K. Choueiri, MD.

Impressive disease-free survival seen with adjuvant pembrolizumab in clear cell RCC

A retrospective analysis presented during the 2021 AUA Annual Meeting provided fresh insight for the ongoing challenge of determining which patients with prostate cancer would respond best to immune checkpoint inhibitors.

Specifically, the study showed that men whose tumors are microsatellite instability (MSI)–high (MSI-H) or mismatch repair–deficient (dMMR) may have a greater response to immune checkpoint blockade compared with patients with high tumor mutational burden (TMB-H).

Of 21 patients with MSI-H/dMMR prostate cancer who had been treated with immunotherapy, most achieved a partial response (n = 9) or stable disease (SD; n = 10) as their best response. In the 7 patients with prostate cancer whose tumors were TMB-H, 5 patients had SD and 2 patients had disease progression.

“Many of these MSI-H/dMMR patients had prolonged and durable responses; on the other hand, no patient with a TMB-high tumor treated with a checkpoint blockade had a response,” lead study author Andrew T. Lenis, MD, a urology fellow at Memorial Sloan Kettering Cancer Center (MSK), said in a virtual presentation during the conference. “MSI-H/dMMR and TMB-H are rare molecular subgroups; approximately 40% of patients with MSI-H/dMMR prostate cancers respond to immune checkpoint blockade.”

Patients who have MSI-H or dMMR prostate cancer, including those with TMB-H tumors that are microsatellite stable (MSS), are eligible for treatment with the PD-1 inhibitor pembrolizumab (Keytruda). Although MSI-H/dMMR and TMB-H are related, they are of biologically distinct molecular subgroups, Lenis said, adding that both phenotypes lead to hypermutated states that allow for neoantigen targets for checkpoint inhibitor–enhanced immune responses.

“Few MSI-high/dMMR and TMB-high prostate cancers were included in the initial studies and the decision to use immune checkpoint blockade is thus guided by small case series,” Lenis explained. “Our objective was to genomically characterize MSI-high/dMMR and TMB-high prostate cancers and evaluate and compare the responses with immune checkpoint blockade.”

In the analysis, investigators retrospectively identified men with prostate cancer who underwent genomic profiling via MSK-IMPACT. To meet the criteria for genomically-identified MSI-H/dMMR, tumors needed to have a MSISensor score of 10 or greater, or a score that is “indeterminant” between 3 and 10 and harbor a deleterious alteration in 

. TMB-H tumors needed to have at least 10 mutations/megabase.

Investigators identified 2813 patients with prostate cancer who were enrolled on the prospective, phase 3 IMPACT trial (NCT00065442) from April 7, 2015 to February 18, 2021. Sixty-four patients (2.9%) were deemed to have MSI-H/dMMR tumors, 32 (1.4%) had TMB-H tumors, and 2146 (95.9%) had MSS/TMB-low (TMB-L) tumors. Patients with inadequate samples were excluded from the analysis.

Across all patients analyzed, the median age was 62 years (range, 56-68), most patients (83.7%) were White, and more than half (53.8%) were never smokers. Patients had either grade 1 (8.2%), 2 (14.1%), 3 (16.1%), 4 (18.7%), or 5 (34.9%) disease; 8.1% of patients’ tumor grades were not available. The prostate-specific antigen (PSA) level at diagnosis was less than 4 (11.2%), between 4 and 10 (39.1%), between 10 and 20 (16.4%), or greater than 20 (27.6%); 5.7% of PSA levels were not identified.

Furthermore, 65.9% of patients had stage N0M0 disease, followed by those with M1 (27.5%) and N1M0 (6.5%) stage disease.

Although no significant differences were observed in age and race between the 3 cohorts, patients with MSI-H or TMB-H tumors were more likely to present at grade 5 at 56.2% and 53.1%, respectively, compared with 34% of those with MSS disease. N1M0 and M1 stage disease were also more prevalent in MSI-H (9.4% and 34.4%, respectively) and TMB-H tumors (15.6% and 18.8%) vs in those with MSS/TMB-L tumors (6.2% and 27.4%).

Lenis added that patients with MSI-H/TMB-H tumors also had higher MSISensor scores and TMB scores.

When comparing responses between the MSI-H/dMMR and TMB-H/MSS subgroups, data showed that although the PSA50 responses appeared similar between the 2 groups, only patients in the MSI-H/dMMR cohort experienced a response to immune checkpoint blockade.

Additionally, the median radiographic progression-free survival was 41 months for those in the MSI-H/dMMR cohort compared with 7 months for patients with TMB-H disease (

Lenis concluded that despite the limited sample size in the analysis, MSI-H/dMMR prostate cancers are more frequent responders, coupled with more durable responses, to immunotherapy compared with TMB-H prostate cancers.

“Genomic comparisons between responders and non-responders to immune checkpoint blockade is ongoing,” he added.

1. Lenis AT, Ravichandran V, Truong H, et al. Response to immune checkpoint blockade in patients with microsatellite instable and high tumor mutational burden prostate cancer. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract MP24-01.

Men whose tumors are microsatellite instability–high or mismatch repair–deficient may have a greater response to immune checkpoint blockade compared with patients with high tumor mutational burden.

Study offers clues on optimal patients for immunotherapy in prostate cancer

Findings from a small, single-arm study of 12 patients showed a 3-month complete response (CR) rate of 42% and 12-month CR rate of 17% in patients with BCG–unresponsive non–muscle invasive bladder cancer (NMIBC) treated with a combination of durvalumab (Imfinzi) and Vicineum (oportuzumab monatox, VB4-845).

The combination treatment was found to be well tolerated. Interim results from the phase 1 trial (NCT03258593) were presented during the 2021 American Urological Assocation Annual Meeting.

In the small, single-arm study of 12 patients, data showed that the 3-month CR rate was 42% and the 12-month CR rate was 17% in this patient population.

“The combination of Vicineum and durvalumab in BCG-unresponsive NMIBC is tolerated well and no new safety signals were identified; the doublet has a similar safety profile to [what is seen with] both agents used individually,” Sandeep Gurram, MD, a urologic oncologist at National Cancer Institute, said in a virtual presentation on the findings. “Further biomarker analysis may help predict which patients will be responders on therapy.”

Vicineum is a recombinant fusion protein made up of an anti-EpCAM linked to a truncated form of 

 exotoxin A. Ninety-eight percent of patients who are refractory to BCG harbor EpCAM overexpression. Previously, Vicineum was evaluated in the 3-cohort, phase 3 VISTA trial (NCT02449239), in which the duration of response in patients who achieved a CR with the agent was 287 days. In a cohort combining all patients with carcinoma in situ (CIS), the 3-month and 12-month CR rates were 40%and 17%, respectively.

Additionally, checkpoint blockade in patients with BCG-unresponsive disease has also elicited clinical activity, providing the rationale to explore both therapies in patients with high-grade NMIBC.

Durvalumab, a PD-L1 inhibitor, was granted an accelerated approval in May 2017 as a treatment for patients with locally advanced or metastatic urothelial carcinoma who have experienced disease progression during or after platinum-containing chemotherapy or who had disease progression within 1 year of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

However, in February 2021, AstraZeneca, the manufacturer of durvalumab, voluntarily withdrew the PD-L1 inhibitor from the US market for this indication following negative findings from the phase 3 DANUBE trial (NCT02516241).

 Results from the study showed that neither durvalumab alone or in combination with tremelimumab met the coprimary end points of overall survival compared with chemotherapy in patients with metastatic urothelial cancer.

“The purpose of this study is to use both agents, durvalumab and Vicineum, in concert,” Gurram said. “Intravesical Vicineum allows for drug cytotoxic effect on urothelial carcinoma, and this allows for increased neoantigen presence, which is subsequently exploited with the use of durvalumab.”

To be eligible for enrollment, patients had to have CIS with or without papillary tumors or high-grade Ta or T1 urothelial cancer that was BCG unresponsive, and their last dose of BCG had to have been received within 1 year. Moreover, patients had to have adequate hepatic and renal function and their ECOG performance status had to be 0 or 1. They could not have previously received treatment with a PD-1/PD-L1 inhibitor and could not have had any history of upper tract or urethral urothelial cancer within the past 2 years.

Patients were treated with 30 mg of Vicineum intravesically as a weekly induction treatment for 12 weeks, followed by maintenance Vicineum given biweekly up until week 52, plus durvalumab at 1500 mg intravenously monthly every 4 weeks for 52 weeks. It was optional to receive Vicineum every other week for an additional 52 weeks, as well as durvalumab every 12 weeks for an additional 52 weeks. Patients were evaluated with cytology and cystoscopy and with an optional biopsy every 3 months.

A safety run-in cohort enrolled 6 to 12 patients before moving onto an expansion cohort of 18 patients. Furthermore, a 3+3 dose de-escalation design was conducted to determine the maximum-tolerated dose (MTD). The primary end point of the trial was safety and tolerability; secondary end points included efficacy, pharmacokinetics, and biomarker analysis.

The median age of patients was 69.5 years (range, 57-82), 92% of patients were male, and all patients were White and non-Hispanic. Most patients (83%) had an ECOG performance status of 0. Twenty-five percent of patients were never smokers, 67% were former smokers, and 8% were current smokers.

The median number of BCG induction courses was 2 (range, 1-4), and at screening, patients had CIS with or without papillary (33%), Ta disease (50%), or T1 disease (17%).

In the safety cohort, all 6 patients enrolled did not experience any dose-limiting toxicities; the MTD was determined to be 30 mg of Vicineum in 50-mL saline.

In the interim analysis with the full study population (n = 12), no dose reductions or discontinuations were reported with either agent. Moreover, no patients stopped being on study because of treatment-related adverse effects (TRAEs). Two patients did come off study because of unrelated medical issues, which included worsening of baseline peripheral vascular disease and cognitive decline secondary to worsening vascular dementia. Both patients were 3-month responders, Gurram noted.

All patients on study experienced any-grade TRAEs, and 25% of patients had grade 3 or higher TRAEs. The most common TRAEs were hematuria (41.7%), renal and urinary disorders (41.7%), urinary tract infection (41.7%), urinary frequency (41.7%), pruritis (33.3%), diarrhea (25%), and rash maculo-papular (25%). Grade 3 or higher TRAEs included hematuria, bladder infection, thromboembolic event, and hyponatremia (8.3% each). No grade 4/5 AEs were observed.

One patient needed systemic corticosteroids for persistent grade 2 diarrhea due to colitis, which was an immune-related event.

Additional data showed that 67% of patients experienced disease progression or recurrence of high-grade NMIBC, and 8.3% had progressed to muscle-invasive bladder cancer. The 1-year cystectomy-free survival rate was 75% and no patients died from their bladder cancer.

In August 2021, the FDA issued a complete response letter to Sesen Bio, the developer of Vicineum, denying the approval of a biologics license application for the treatment of patients with BCG-unresponsive NMIBC.

The agency is requesting additional clinical and statistical data and analyses, and Chemistry, Manufacturing and Controls issues were noted in the letter that need to be addressed.

1. Gurram S, Bellfield S, Dolan R, et al. Interim analysis of a phase I single-arm study of the combination of durvalumab (MEDI4736) and Vicineum (oportuzumab monatox, VB4-845) in subjects with high-grade non-muscle-invasive bladder cancer previously treated with Bacillus Calmette-Guerin. Presented at: 2021 AUA Annual Meeting; September 10-13, 2021; Virtual. Abstract PD09-04

2. Sesen Bio reports positive, preliminary data update from phase 3 VISTA trial for high-risk non-muscle invasive bladder cancer. News release. Sesen Bio. August 8, 2019. Accessed September 11, 2021. https://bit.ly/3l9guFE

3. Durvalumab (Imfinzi). News release. FDA. May 1, 2017. Accessed September 11, 2021. https://bit.ly/3qLyTKd

4. Voluntary withdrawal of Imfinzi indication in advanced bladder cancer in the US. News release. AstraZeneca. February 22, 2021. Accessed September 11, 2021. http://bit.ly/2P2KjLN

5. Sesen Bio receives complete response letter from FDA for Vicineum (oportuzumab monatox-qqrs). News release. Sesen Bio. August 13. 2021. Accessed September 1, 2021. https://bit.ly/3xQdt1e

“The combination of Vicineum and durvalumab in BCG-unresponsive NMIBC is tolerated well and no new safety signals were identified; the doublet has a similar safety profile to [what is seen with] both agents used individually,” says Sandeep Gurram, MD.

Combination treatment with durvalumab/vicineum elicits complete responses in high-grade NMIBC

Posthoc analyses from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) of patients with advanced urothelial cancer showed that the overall survival (OS) benefit with frontline avelumab (Bavencio) maintenance observed in the overall population was sustained across multiple previously unreported subgroups.

The JAVELIN Bladder 100 trial included patients who progressed on frontline platinum-containing chemotherapy. Data from the posthoc analyses, which were shared during the 2021 ASCO Annual Meeting, showed that progression-free survival (PFS) and OS improvements were seen in patients with upper tract or lower tract disease; metastatic disease, unresectable locally advanced disease, or lymph node–only disease; PD-L1–positive tumors who received frontline gemcitabine/carboplatin; and The Cancer Genome Atlas (TCGA)–defined tumor genomic subtypes, with the exception of those with the luminal subtype (HR, 1.01; 95% CI, 0.403-2.509). 

Additionally, an analysis of key immune biomarkers by TCGA subtype did not predict benefit with avelumab in the frontline maintenance setting.

“Overall, it doesn’t appear that this molecular TCGA analysis is able to identify the ‘winners and the losers’ associated with maintenance avelumab. This is important because it means we need to move to different types of biomarkers in the future,” Thomas Powles, MBBS, MRCP, MD, lead study author, professor of genitourinary oncology, and director of Barts Cancer Centre, said in a presentation during the meeting. “We’ve added something to the field today. I believe that biomarker-positive [and] carboplatin subgroups of patients are relevant, and I also think that the molecular analysis builds on what we know and points us in a different direction of biomarker development in the future.”

In the phase 3 JAVELIN Bladder 100 study, first-line maintenance with avelumab plus best supportive care (BSC) was found to significantly improve survival versus BSC alone in patients with advanced urothelial cancer that did not progress on frontline platinum-based chemotherapy. Overall, the median OS was 21.4 months with the addition of avelumab and 14.3 months with BSC alone, leading to a 31% reduction in the risk of death (HR, 0.69; 95% CI; 0.56-0.86; 1-sided 

Based on these findings, the FDA approved frontline maintenance with avelumab plus BSC in June 2020 for use in this patient population.

Another analysis on JAVELIN Bladder 100 showed that the survival benefit achieved with this approach was seen in all analyzed subgroups, including those who received cisplatin/gemcitabine or carboplatin/gemcitabine as frontline chemotherapy.

In the trial, patients with locally advanced or metastatic urothelial cancer that had not progressed on frontline chemotherapy were randomized 1:1 to receive frontline maintenance with avelumab plus BSC (n = 350) or BSC alone (n = 350) until disease progression, unacceptable toxicity, or withdrawal. The data cutoff date was October 21, 2019.

The primary end point of the trial was OS in the overall study population and in those with PD-L1–positive tumors. The post-hoc analyses were conducted in exploratory subgroups, which were defined as: primary tumor site (upper vs lower urinary tract), type of advanced disease (metastatic or unresectable locally advanced disease prior to chemotherapy, or lymph node–only disease following chemotherapy), and TCGA subtype (basal squamous, luminal, luminal infiltrated, or luminal papillary).

The breakdown of the site of primary tumor and type of advanced disease was as follows: upper urinary tract (avelumab/BSC, n = 106; BSC, n = 81), lower urinary tract (avelumab/BSC, n = 244; BSC, n = 269), metastatic disease (avelumab/BSC, n = 216; BSC, n = 215), unresectable locally advanced disease prior to chemotherapy (n = 133 in both arms), and lymph node–only disease after chemotherapy (avelumab/BSC, n = 48; BSC, n = 39).

Additionally, patients with PD-L1–positive tumors who received frontline gemcitabine/carboplatin were analyzed as a specific population of interest. Seventy-four of these patients received avelumab plus BSC vs 54 who received BSC alone.

The baseline characteristics were well balanced between the arms of the subgroups of interest.

The PFS and OS benefits were observed irrespective of primary tumor site or type of advanced disease. There was, however, a greater difference of OS outcomes in those with lower tract primary tumors (HR, 0.62; 95% CI, 0.477-0.802), unresectable locally advanced disease (HR, 0.40; 95% CI, 0.265-0.617), or lymph node–only disease following chemotherapy (HR, 0.55; 95% CI, 0.259-1.152), but the investigators noted that the number of patients and events were small.

The PFS outcomes were similar with avelumab/BSC vs BSC alone in these exploratory subgroups: lower tract (HR, 0.54; 95% CI, 0.434-0.673), locally advanced and unresectable disease (HR, 0.44; 95% CI, 0.315-0.606), and lymph node–only disease (HR, 0.37; 95% CI, 0.205-0.669). Similar to the OS data, the luminal subtype showed the least benefit of the other TCGA subtypes (HR, 0.73; 95% CI, 0.355-1.500).

In the basal squamous subgroup, the median OS was 24.0 months (95% CI, 16.0–not evaluable [NE]) and 17.9 months (95% CI, 12.7–NE) with avelumab/BSC (n = 46) and BSC alone (n = 44), respectively (HR, 0.62; 95% CI, 0.326-1.187). In the luminal subgroup, the median OS was 23.8 months (95% CI, 12.5-NE; n = 30) and NE (95% CI, 14.3–NE; n = 26), respectively (HR, 1.01; 95% CI, 0.403-2.509).

In the luminal-infiltrated group, the median OS was 19.9 months (95% CI, 18.2–NE) with avelumab/BSC (n = 143) and 14.3 months (95% CI, 12.8-18.6) with BSC alone (n = 143; HR, 0.68; 95% CI, 0.481-0.968). Finally, in the luminal papillary subgroup, the median OS was 22.5 months (95% CI, 18.2-26.0) with avelumab/BSC (n = 61) compared with 13.4 months (95% CI, 10.1-NE) with BSC alone (n = 63; HR, 0.63; 95% CI, 0.370-1.079).

Further data showed that longer outcomes were seen in the avelumab arm in patients with PD-L1–positive disease who received frontline gemcitabine/carboplatin for PFS (HR, 0.61; 95% CI, 0.390-0.958) and OS (HR, 0.67; 95% CI, 0.393-1.137). These data were consistent with the overall study population.

Specifically, the median OS was 24.0 months (95% CI, 18.6–not estimable [NE]) with avelumab plus BSC and 16.1 months (95% 9.4–NE) with BSC alone; the median PFS was 3.7 months (95% CI, 2.0-12.0) and 2.4 months (95% CI, 1.9-3.7), respectively.

“These data really support further the approach of giving chemotherapy to get control of the disease and then maintaining that control with maintenance avelumab rather than giving frontline immune therapy, in my opinion, and I think this does really add to the field,” Powles said.

The authors also noted that PD-L1 expression on tumor cells and CD8–positive cells in the total tumor area were higher in the basal squamous subtype vs other TCGA subtypes.

1. Powles T, Petrylak DP, Park, SH, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial. 

. 2021;39(suppl 15):4520. doi:10.1200/JCO.2021.39.15_suppl.4520

2. Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. 

. 2020;383(13):1218-1230. doi:10.1056/NEJMoa2002788

3. Grivas P, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100. 

. 2020;31(suppl 4):S550-S550. doi:10.1016/annonc/annonc274

Avelumab is approved by the FDA for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

Gina Mauro

Articles

Impressive disease-free survival seen with adjuvant pembrolizumab in clear cell RCC

Study offers clues on optimal patients for immunotherapy in prostate cancer

Combination treatment with durvalumab/vicineum elicits complete responses in high-grade NMIBC

Posthoc data show depth of frontline avelumab maintenance OS benefit in bladder cancer