Interim analysis of ibrutinib plus paclitaxel for patients with advanced urothelial carcinoma previously treated with platinum-based chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4522-4522
Author(s):  
Daniel E. Castellano ◽  
Rafael Morales-Barrera ◽  
Ignacio Duran ◽  
Bhumsuk Keam ◽  
Ik Joo Chung ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Interim Analysis ◽  
Checkpoint Inhibitors ◽  
Geometric Mean ◽  
Major Hemorrhage ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Phase 1B ◽  
Advanced Urothelial Carcinoma

4522 Background: Patients (pts) with advanced urothelial carcinoma (aUC) who progressed after platinum-based chemotherapy (PBCT) have a median overall survival (OS) of ~6 mo on CT and 8-10 mo on novel immune checkpoint inhibitors (ICIs). Treatment (tx) with ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton’s tyrosine kinase (BTK) with immunomodulatory properties, plus paclitaxel (pac) may improve outcomes for pts with aUC. Methods: Pts with aUC who had 1-2 prior tx (≥1 PBCT and/or ICIs) formed one cohort of this phase 1b/2 study. Recommended phase 2 dose per phase 1b was ibr 840 mg/d + weekly pac 80 mg/m2 in 21-d cycles; starting ibr dose of 560 mg/d. nanoString gene expression assay (NanoString Technologies) was used for preliminary assessment of ibr-targeted kinases in baseline tumor biopsies. Results: This interim analysis included the first 29 pts treated (ibr 840/560 mg/d, n = 25/4; median age 67 y). 52% had 2 prior regimens (prior PD-L1 inhibitors, 100%). Median time on study/tx was 7.2/2.3 mo (max tx: 11.5 mo). Unconfirmed overall response rate (ORR) was 41% (complete/partial response: 10%/31%). Disease control rate was 62%. ORR was 71% for 7 pts with only lymph node metastases; ORR was 36% for 14 pts with 1 prior tx and 47% for 15 pts with 2 prior tx. Median duration of response was 4.2 mo (90% CI: 1.9-7.1). Median progression-free survival was 3.6 mo (90% CI: 1.6-5.4). Median OS was 14.7 mo (90% CI: 7.7-15.9). Follow-up is ongoing for durability/survival with 6 pts alive without progression, including 4 still on ibr. 76% of pts had grade ≥3 adverse events (AEs); 4 discontinued ibr + pac due to AEs and 1 had major hemorrhage. Pac exposure was not impacted by ibr; pac geometric mean Cmax (2066 ng/mL) and AUC0-∞ (3813 ng·h/mL) were consistent with historical data. Preliminary tumor biopsy data showed a nonsignificant trend of higher BTK/ITK/BMX expression in tx responders; analyses are ongoing. Conclusions: Ibr + pac shows promising results for ORR/OS in pts with aUC previously treated with PBCT and ICIs. No unexpected safety signals were seen; ibr + pac seemed tolerable. Follow-up of these and additional pts will support the activity and safety of ibr + pac in this study. Clinical trial information: NCT02599324.

Interim analysis of ibrutinib plus paclitaxel for patients with metastatic urothelial carcinoma previously treated with platinum-based chemotherapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 365-365
Author(s):  
Daniel E. Castellano ◽  
Rafael Morales-Barrera ◽  
Ignacio Duran ◽  
Bhumsuk Keam ◽  
Ik Joo Chung ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Interim Analysis ◽  
Checkpoint Inhibitors ◽  
Geometric Mean ◽  
Tumor Biopsy ◽  
Major Hemorrhage ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Phase 1B

365 Background: In patients (pts) with advanced urothelial carcinoma (aUC) who progressed after platinum-based chemotherapy (CT), median overall survival (OS) is ~6 mo with CT and 8-10 mo with novel immune checkpoint inhibitors (ICIs). Ibrutinib (ibr), a first-in-class, once-daily, inhibitor of Bruton’s tyrosine kinase (BTK) with immunomodulatory properties, plus paclitaxel (pac) may be an effective treatment (tx) for pts with UC. Methods: One cohort in this phase 1b/2 study assessed ibr + pac in pts who had 1-2 prior tx (≥1 platinum-based and/or ICIs) with aUC. Recommended phase 2 dose per Phase 1b was ibr 840 mg/d + weekly pac 80 mg/m2 in 21-d cycles; starting ibr dose: 560 mg/d. Preliminary BTK/other kinase assessment in baseline tumor biopsies was done by NanoString gene expression assay. Results: Based on interim analysis of the first 29 pts treated (ibr 840/560 mg/d, n = 25/4), median time on study/ tx was 7.2/2.3 mo (max tx: 11.5 mo). Median age was 67 y; 52% had 2 prior regimens (prior PDL-1 inhibitors, 100%). Unconfirmed ORR was 41% (complete/partial response: 10%/31%) and disease control rate was 62%. ORR was 71% for subset of 7 pts with only lymph node metastases, and 36% for 14 pts with 1 prior tx and 47% for 15 with 2 prior tx. Median duration of response was 4.2 mo (90% CI: 1.9, 7.1). Median PFS was 3.6 mo (90% CI: 1.6, 5.4) and median OS was 14.7 mo (90% CI: 7.7, 15.9). Follow-up for durability/survival is ongoing with 6 pts alive without progression, with 4 still on ibr tx. 76% of pts had grade ≥3 adverse events (AEs); 4 discontinued ibr + pac due to AEs and 1 had major hemorrhage. Pac exposure was not impacted by ibr; pac geometric mean Cmax (2066 ng/mL) and AUC0-∞ (3813 ng.h/mL) were consistent with historical data. Preliminary tumor biopsy data showed a non-significant trend of higher BTK/ITK/BMX expression in responders; analyses are ongoing for ibr-targeted kinases. Conclusions: These results indicate that ibr + pac shows promising results for ORR and OS in pts with aUC previously treated with platinum-based CT and ICIs. There were no unexpected safety signals; ibr + pac seemed tolerable. Follow up of these and additional pts will support the efficacy and safety of ibr + pac in this study. Clinical trial information: NCT02599324.

265 Phase 1b study of avelumab + M9241 (NHS-IL12) in patients with advanced solid tumors: interim analysis results from a urothelial carcinoma (UC) dose-expansion cohort

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A291-A291
Author(s):  
Jean-Laurent Deville ◽  
Alain Ravaud ◽  
Marco Maruzzo ◽  
Theodore Gourdin ◽  
Michele Maio ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Interim Analysis ◽  
Maintenance Treatment ◽  
Advanced Solid Tumors ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Phase 1B ◽  
Expansion Cohort

BackgroundAvelumab is an anti–PD-L1 monoclonal antibody approved for the treatment of advanced UC after disease progression during or following platinum-based chemotherapy and as maintenance treatment in patients whose disease has not progressed with first-line platinum-based chemotherapy.1–3 M9241 is an immunocytokine composed of 2 heterodimers of IL-12 fused to the heavy chains of a human antibody targeting DNA released from necrotic tumor cells.4 During dose-escalation, avelumab + M9241 was well tolerated and showed promising antitumor activity in patients with advanced solid tumors, including 2 objective responses in patients with UC.5 We report on an interim analysis of efficacy and safety from the dose-expansion part of JAVELIN IL-12 (NCT02994953).MethodsEligible patients had locally advanced or metastatic UC that had progressed on first-line therapy, were aged =18 years, had an Eastern Cooperative Oncology Group performance status of 0/1, and were immune checkpoint inhibitor naive. Patients received the recommended phase 2 dose5 of avelumab 800 mg intravenously once weekly (QW) in combination with M9241 16.8 µg/kg subcutaneously Q4W for the first 12 weeks, then continued the combination with avelumab Q2W. The primary endpoints were confirmed best overall response (BOR) per investigator assessment (RECIST 1.1) and safety. The expansion cohort followed a 2-stage design. During stage 1 (single-arm part of the study), 16 patients were enrolled and treated. A futility analysis based on BOR was planned to determine if stage 2 (randomized controlled part of the study) would be initiated.ResultsAt data cut-off (Jun 3, 2020), 16 patients had received avelumab + M9241 for a median duration of 8 weeks (range, 4.0–25.0 weeks). No complete or partial responses were observed; the study failed to meet the criterion (>2 responders) to initiate stage 2. Two patients (12.5%) had stable disease, 13 (81.3%) had progressive disease, and 1 (6.3%) was not evaluable. Any-grade treatment-related adverse events (TRAEs) occurred in 15 patients (93.8%); the most common (in =4 patients) were pyrexia (50.0%), nausea (37.5%), asthenia (31.3%), anemia (25.0%), and hyperthermia (25.0%); grade 4 gamma-glutamyltransferase increased occurred in 1 patient (6.3%). No TRAEs led to death. Pharmacodynamic effects on the peripheral immune system and results of pharmacokinetic and biomarker analyses will also be reported.ConclusionsThe predefined efficacy criterion to proceed to stage 2 was not met. The combination was well tolerated; no new safety signals emerged and the profile was consistent with the dose-escalation part of the study.5Trial RegistrationNCT02994953Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesBavencio(avelumab) injection [package insert]. Rockland, MA: EMD Serono, Inc; New York, NY: Pfizer Inc; 2020.Health Canada. https://www.canada.ca/en/health-canada.html. Accessed July 31, 2020.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed July 31, 2020.Fallon J, Tighe R, Kradjian G, et al. The immunocytokine NHS-IL12 as a potential cancer therapeutic. Oncotarget. 2014;5:1869–1884.Strauss J, Vugmeyster Y, Sznol M, et al. Phase 1b, open-label, dose escalation study of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumours. Ann Oncol. 2019;30(5 Suppl):Abstract 4062.

Impact of immune-related adverse events on survival in patients with metastastic urothelial carcinoma treated with immune-checkpoint inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4531-4531 ◽  
Author(s):  
Rafael Morales-Barrera ◽  
Cristina Suarez Rodriguez ◽  
Macarena Gonzalez ◽  
Javier Ros ◽  
Maria Eugenia Semidey ◽  
...  
Keyword(s):  
Adverse Events ◽  
Urothelial Carcinoma ◽  
T Cell Activation ◽  
Checkpoint Inhibitors ◽  
Strong Predictor ◽  
Immune Checkpoints ◽  
Rank Test ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Grade 3

4531 Background: Immune-checkpoints inhibitors (ICIs) represents the standard of care for platinum-pretreated advanced urothelial cancer patients (pts). By enhancing T-cell activation, a unique spectrum of inflammatory side effects has emerged, also known as immune-related adverse events (irAEs). Data regarding the association between irAEs and pts outcomes are conflicting. Here we conducted a retrospective analysis to investigate the association between irAEs profile and disease outcome in metastastic urothelial carcinoma (mUC) pts. Methods: Medical records from pts with mUC included in clinical trials between July 2013 and June 2018 and treated with ICIs were reviewed. Pts previously treated with platinum-based chemotherapy or cisplatin ineligible pts who had not been previously treated with chemotherapy were included. Clinical responses were assessed as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST v1.1. Adverse events were graded based CTCAE v4.03. Overall survival (OS) was calculated from the date of initiation of ICI to the date of death. X2 test was used to determine differences in rates. OS was estimated using Kaplan-Method and long rank test was used to assess differences between groups. All analyses were performed using SPSS v21. Results: From a total of 52 pts, 44 (84.6%) were treated with ICI monotherapy and 8 (15.3%) in combination (anti-CTLA4 or targeted therapy). Median age was 65 years, 42 pts (80.8%) were male, 44 patients (84.6%) had ECOG PS 0-1, 14 pts (26.9%) had liver metastasis. Overall irAEs were observed in 30 pts (57.7%) and 10 pts (19.2%) developed grade 3/4 irAES. Most common grade 3/4 irAEs were diarrhea (6.6%), rash (6.6%) and hepatitis (6.6%). Disease control rate (CR [26%]+PR[33%]+SD[20%]) was higher for patients with irAEs compared to those patients who did not developed irAEs (CR [13.6%]+PR[0%]+SD[22.7%], this difference was statically significant (P = 0.002). Median OS was 11.23 mo (CI 95%, 3.76-18.70) for the overall cohort, while median OS was 21.91 mo for those patients with irAEs compared to 6.47 mo in patients who did not developed irAEs (P = 0.004). Conclusions: In this analysis we found that the development of irAEs was a strong predictor of improved OS in mUC patients treated with ICI.

scholarly journals Approved checkpoint inhibitors in bladder cancer: which drug should be used when?

2018 ◽  
Vol 10 ◽  
pp. 175883591878831 ◽  
Author(s):  
Pooja Ghatalia ◽  
Matthew Zibelman ◽  
Daniel M. Geynisman ◽  
Elizabeth Plimack
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
United States Food ◽  
Phase Iii Trials ◽  
Metastatic Urothelial Carcinoma ◽  
States Food ◽  
Advanced Urothelial Carcinoma ◽  
Line Setting

The treatment of advanced metastatic urothelial carcinoma has recently evolved with the approval of five checkpoint inhibitors. In the second-line setting, in patients who have progressed on cisplatin-based chemotherapy, pembrolizumab, atezolizumab, durvalumab, nivolumab and avelumab are United States Food and Drug Administration (FDA) approved. In cisplatin-ineligible patients, atezolizumab and pembrolizumab are the FDA-approved checkpoint inhibitors. Here we describe the updated clinical efficacy of these checkpoint inhibitors in the treatment of advanced urothelial carcinoma and then suggest how they can be sequenced in the context of available chemotherapeutic options. For cisplatin-eligible patients, platinum-based chemotherapy remains the standard first-line treatment. For patients progressing on platinum-based therapy, phase III trials have been performed comparing pembrolizumab and atezolizumab separately with standard chemotherapy, and results favor the use of pembrolizumab.

Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with advanced urothelial carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 519-519
Author(s):  
Seung-Hoon Beom ◽  
Sun Young Rha ◽  
Joong Bae Ahn ◽  
Sang Joon Shin
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma

519 Background: Immune checkpoint inhibitors (ICI) are active in patients with advanced urothelial carcinoma which progressed to platinum-based chemotherapy. Recent data suggest that exposure to ICI improves response to salvage chemotherapy (SCT) in several cancer types. Here we evaluated whether PD-1/PD-L1 inhibitors affect the antitumor effects of SCT after ICI in patients with urothelial carcinoma. Methods: A retrospective study was conducted at Yonsei Cancer Center. Eligibility criteria were patients who received at least one SCT as 3rd-line or beyond, following progression after platinum-based chemotherapy and ICI and for whom efficacy data were available between January 2017 and September 2019. We evaluated efficacy outcomes to each therapy, including ORR by RECIST version 1.1, progression-free survival (PFS), and overall survival (OS). Results: In total, 35 patients met the inclusion criteria and were included in the analyses. ICIs were given as monotherapy and they were administrated as second-line in 48% and as later line in 52%. Twenty-six patients (74%) received a anti-PD-L1 inhibitor and 9 (26%) did a anti-PD-1 inhibitor. SCT included single paclitaxel (60%), MVAC (26%), gemcitabine/platinum combination (9%), and pemetrexed (6%). The ORR to SCT was 26%. Among 9 patients who received MVAC, 5 (55.5%) achieved a partial response. Median progression-free survival was 2.5 months and median overall survival was 7.8 months. A number of prior chemotherapy regimens was associated with response to SCT on univariate analysis. Conclusions: In urothelial cancer patients, the confirmed ORR (26%) to SCT after ICI exposure was higher as compared to historical data from the pre-ICI era. These data indicate that anti–PD-1/PD-L1 inhibitors could make tumors more vulnerable to subsequent chemotherapy.

Preliminary analysis of a phase II, multicenter, randomized, active-control study to evaluate the efficacy and safety of eganelisib (IPI 549) in combination with nivolumab compared to nivolumab monotherapy in patients with advanced urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 436-436
Author(s):  
Piotr Tomczak ◽  
Lazar Popovic ◽  
Philippe Barthelemy ◽  
Aleksander Janicic ◽  
Elena Sevillano Fernandez ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Preliminary Data ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Suppressor Cells ◽  
Progression Free Survival ◽  
Transaminase Elevation ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma ◽  
To Receive

436 Background: Inhibition of the PD-1 pathway has demonstrated clinical benefit in metastatic urothelial carcinoma (mUC); however, response rates of 15% to 29% highlight the need for more effective therapies, especially for PD-L1- patients. Eganelisib is a first-in-class, novel, oral agent which selectively inhibits PI3K-γ, with the goal of improving the immune response to checkpoint inhibitors (CPI). Methods: Eligible patients (pts) with mUC who progressed on > 1 platinum-based chemotherapy regimen and were CPI naïve were enrolled. Pts were randomized 2:1 to receive eganelisib in combination with nivolumab (EN) or placebo with nivolumab (PN). Pts were stratified by baseline circulating monocytic myeloid derived suppressor cells (mMDSC) level. The primary endpoint was objective response rate (ORR) per RECIST v1.1 in pts with high baseline mMDSC levels. Other endpoints included ORR, progression free survival (PFS) and overall survival (OS) in all pts and PD-L1 +/- pts. Results: We report preliminary data (as of 9/1/2020) for the first 49 pts with 33 randomized to receive EN and 16 PN. Preliminary ORR/PFS is presented in the table below. Except for the mMDSC high subgroup, ORR and PFS were improved in the EN arm compared to the PN arm. The duration of exposure was a median of 15 weeks for EN and 11 for PN. Most common all-Gr AEs (EN vs PN %) were pyrexia (33 vs 0), decreased appetite (30 vs 19), pruritis (24 vs 6), rash (24 vs 6), asthenia (21 vs 31), and transaminase elevation (21 vs 6). Most common Gr≥3 AEs (EN vs PN %) include hepatotoxicity (15 vs 0), transaminase elevation (12 vs 6), and rash (9 vs 0). Following an early safety review, eganelisib dose was reduced from 40 to 30 mg, resulting in a reduction of hepatic AEs. Conclusions: Preliminary data demonstrates that the combination of eganelisib, once reduced to 30 mg, and nivolumab was well tolerated with hepatic and skin-related toxicities more common in the EN arm. When compared to PN, the combination demonstrated an improved ORR and PFS, especially in the PD-L1- subset. Updated efficacy, including PFS and OS, safety and translational data will be presented. Clinical trial information: NCT03980041 . [Table: see text]

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

281 JAVELIN Medley VEGF: phase 2 study of avelumab + axitinib in patients with previously treated non-small cell lung cancer (NSCLC) or treatment naive, cisplatin-ineligible urothelial cancer (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A307-A307
Author(s):  
Gabriella Galffy ◽  
Iwona Lugowska ◽  
Elena Poddubskaya ◽  
Byoung Chul Cho ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Maintenance Treatment ◽  
Locally Advanced ◽  
Small Cell Lung ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Open Label Phase ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3

BackgroundAvelumab, a human anti–PD-L1 monoclonal antibody, has shown a manageable safety profile and antitumor activity in multiple tumor types, including platinum-resistant metastatic or recurrent NSCLC,1 and is approved for patients with locally advanced or metastatic UC who have progressed after ≥1 previous line of platinum-based chemotherapy2 3 and as maintenance treatment for those who have not progressed with platinum-based chemotherapy.4 JAVELIN Medley VEGF (NCT03472560) evaluated the efficacy and safety of avelumab + axitinib, a potent inhibitor of VEGFR 1, 2, and 3, in patients with advanced or metastatic NSCLC or UC.MethodsEligible patients with NSCLC had received ≥1 prior platinum-containing therapy and ≤2 prior lines of systemic therapy for locally advanced or metastatic disease; patients with UC were treatment naive in the locally advanced or metastatic setting and ineligible for cisplatin-containing chemotherapy. Patients were immune checkpoint inhibitor naïve and received avelumab 800 mg intravenously every 2 weeks + axitinib 5 mg orally twice daily. The primary endpoint was confirmed objective response (OR) per investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS) and safety. PD-L1 expression was assessed in baseline tumor samples (Ventana SP263 assay). Data have not undergone standard quality checks and are subject to change due to COVID-19–related healthcare burden.ResultsA total of 41 patients with NSCLC and 20 with UC received avelumab + axitinib. The confirmed OR rate was 31.7% (95% CI, 18.1–48.1) in the NSCLC cohort and 10% (95% CI, 1.2–31.7) in the UC cohort (all partial responses); 16 patients (39.0%) and 5 (25.0%) had stable disease, respectively. Responses were observed regardless of PD-L1 expression status. Median PFS was 5.5 months (95% CI, 2.5–7.0) in the NSCLC cohort and 2.3 months (95% CI, 1.8–5.6) in the UC cohort. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 24 patients (58.5%) in the NSCLC cohort; the most common was hypertension (n=7 [17.1%]). Grade ≥3 TRAEs occurred in 9 patients (45.0%) in the UC cohort; the most common were amylase increased, asthenia, decreased appetite, and palmar-plantar erythrodysesthesia syndrome (n=2 [10%] each). One patient in each cohort experienced a TRAE that led to death (gastric perforation and urinary bladder hemorrhage).ConclusionsAvelumab + axitinib showed antitumor activity and a manageable safety profile in patients with advanced or metastatic NSCLC or UC consistent with findings from studies of each drug alone and in combination.Trial RegistrationNCT03472560Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesGulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017;18:599–610.Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 2018;19:51–64.Bavencio(avelumab) injection. [package insert] Darmstadt, Germany: Merck KGaA; 2019.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed August 19, 2020.

scholarly journals Cisplatin- Versus Non–Cisplatin-based First-Line Chemotherapy for Advanced Urothelial Carcinoma Previously Treated With Perioperative Cisplatin

2016 ◽  
Vol 14 (4) ◽  
pp. 331-340 ◽  
Author(s):  
Jennifer A. Locke ◽  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Patrizia Giannatempo ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
First Line ◽  
Previously Treated ◽  
Advanced Urothelial Carcinoma ◽  
Line Chemotherapy
Sign in / Sign up

Export Citation Format

Share Document