Search

Background Image-guided therapies (IGTs) are commonly used in oncology, but their role in adrenocortical carcinoma (ACC) is not well defined. Materials and Methods A retrospective review of patients with ACC treated with IGTs. We assessed response to therapy using RECIST v1.1, time to next line of systemic therapy, disease control rate (DCR), local tumor progression-free survival (LTPFS), and complications of IGTs (based on the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0). Results Our cohort included 26 patients (median age 56 years [range 38-76]; n  = 18 female) who had 51 IGT sessions to treat 86 lesions. IGTs modalities included cryoablation (n  = 49), microwave ablation (n  = 21), combined microwave and bland trans-arterial embolization (n  = 8), bland trans-arterial embolization alone (n  = 3), radio-embolization (n  = 3), and radiofrequency ablation (n  = 2). DCR was 81.4% (70 out of 86), of which 66.3% of tumors showed complete response, 18.6% showed progressive disease, 8.1% showed partial response, and 7.0% showed stable disease. LTPFS rates were 73% and 63% at 1 and 2 years, respectively. Fourteen lesions underwent re-ablation for incomplete response on initial treatment. Sixteen patients (61.5%) received new systemic therapy following IGTs, with a median time to systemic therapy of 12.5 months (95% CI: 8.6 months upper limit not reached). There was 1 reported CTCAE grade 3 adverse event (biloma) following IGT. Conclusions IGT use in properly selected patients with ACC is safe and associated with prolonged disease control and delay in the need for systemic therapy. [ABSTRACT FROM AUTHOR]

Background Tivozanib has been approved as a third-line or later therapy for advanced renal cell carcinoma based on the TIVO-3 trial, which was conducted before immune checkpoint therapies (ICT), cabozantinib, and lenvatinib/everolimus became incorporated in the current sequential treatment paradigm for advanced clear cell RCC (ccRCC). Methods We performed a retrospective study of patients with advanced ccRCC treated with tivozanib at MD Anderson Cancer Center during 6/2021-7/2023. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed overall response rate (ORR), clinical benefit rate (CBR) [percentage of all treated patients who achieved radiologic response or stable disease (SD) for ≥ 6 months], progression-free survival (PFS), overall survival (OS), and safety. Results Of 30 analyzed patients, 23% had performance status ≥ 2; 47% had International Metastatic RCC Database Consortium (IMDC) poor-risk disease. Median number of prior therapies was 4 (range 1-8). All patients received prior ICT, 87% cabozantinib and 60% lenvatinib ± everolimus. Of 26 evaluable patients, 2 patients had confirmed partial response (ORR 7.7%); 5 patients had SD for ≥ 6 months (CBR 23.3%). Median PFS was 3.8 months (range 0.7-13.9); median OS was 14.1 months (range 0.3-28.5). Fifteen patients (50%) had ≥ 1 treatment-related adverse event (TRAE). There were 6 grade ≥ 3 TRAEs [hypertension, congestive heart failure (3), mucositis, and GI perforation (grade 5)]. Conclusions In this cohort of heavily pretreated patients with advanced ccRCC, tivozanib yielded a modest clinical benefit in a minority of patients who received prior ICT, cabozantinib, and lenvatinib ± everolimus. TRAEs were consistent with previously published reports. [ABSTRACT FROM AUTHOR]

Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma.sup.1,2, with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy.sup.2. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathological complete response rate of 17%.sup.2. Here we report on the first pilot combination neoadjuvant trial (NCT02812420) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high-risk features (n = 28). High-risk features were defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis and/or high-grade upper tract disease.sup.3-5. The primary endpoint was safety and we observed 6 of 28 patients (21%) with grade [greater than or equal to]3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (n = 4), hepatitis and colitis (n = 2). We also observed pathological complete response of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (n = 24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment. Neoadjuvant combination of immune checkpoint therapy in patients with cisplatin-ineligible bladder cancer achieves clinical efficacy and uncovers immune features as potential predictive biomarkers of treatment response., Author(s): Jianjun Gao [sup.1] , Neema Navai [sup.2] , Omar Alhalabi [sup.3] , Arlene Siefker-Radtke [sup.1] , Matthew T. Campbell [sup.1] , Rebecca Slack Tidwell [sup.4] , Charles C. Guo [...]

Purpose: We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations. Materials and Methods: Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth x 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and posttrial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel. Results: From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9). Conclusions: In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs. [ABSTRACT FROM AUTHOR]

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes. [ABSTRACT FROM AUTHOR]

Background Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. Patients and Methods Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. Results 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for S + R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. Conclusions A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation. [ABSTRACT FROM AUTHOR]