Background:Glioblastoma confers a bleak prognosis, with median survival of less than a year. This trial evaluated whether addition of the CTLA-4 immune checkpoint inhibitor ipilimumab to standard therapy improves survival in patients with recently diagnosed glioblastoma. Methods:Ipi-Glio was a stratified randomized, open-label, multicenter, academic phase II study. Patients with recently diagnosed de novo glioblastoma following completion of chemoradiotherapy were randomized 2:1 to ipilimumab + temozolomide (Arm A) vs temozolomide alone (Arm B), stratified to extent of surgery and MGMT promotor methylation. Primary endpoint was overall survival. Secondary endpoints included progression-free survival at 18 months, overall survival at 3 years, and toxicity (≥Grade 3). Results:One hundred nineteen patients were randomized (79 to Arm A, 40 to Arm B). Patient characteristics (Arm A vs B): median age 57 vs 49 years; male sex 70 vs 65%, gross total resection 61 vs 60%, tumor MGMT promotor methylation 39 vs 40%. Median overall survival was 18 months (60% CI 16.0, 23.9) in Arm A vs 23.0 months (17.3, 26.4) in Arm B (adjusted HR 1.09, 60% CI 0.86,1.38, one-sided P = .62; logrank P = .75). Progression-Free Survival: 10.8 vs 12.5 months (Arm A vs B) (adjusted HR 1.34, 1.06-1.68, one-sided P = .86;logrank P = .42). Grade 3 or above adverse events: 53% Arm A vs 43% Arm B (P = .27). Conclusions:No benefit was observed with the addition of ipilimumab to temozolomide in patients with recently diagnosed glioblastoma following chemoradiotherapy. This study does not support further investigation of this regimen in this setting. Trial Registration:ISRCTN84434175 (www.isrctn.com/ISRCTN84434175).

Background: The treatment of hormone receptor-positive early breast cancer (HR+ EBC) in patients who are unfit for or decline radical treatment, requires careful consideration of tumor parameters against functional status, comorbidities, and quality of life. In this study, we review the outcomes of patients treated with primary endocrine therapy (PET) in a single UK center. Methods: This is a retrospective observational single institution study looking at patients with HR+ EBC who were not suitable for radical treatment options. Investigators reviewed clinical assessments, tumor characteristics and serial ultrasound measurements for all patients treated with PET to identify the survival outcomes and tumor response measurements, using Kaplan-Meier graphs and RESIST 1.1 criteria respectively. Results: Sixty-one patients with a median age of 82 years (range, 27-97 years) were followed up over an average of 7 years (range, 2-13 years). Seventy-nine percent were commenced on letrozole first line. The majority of patients had lower-risk features; 82% oestrogen receptor (ER) and progesterone receptor (PR) positive, 88% unifocal, 85% T1 or T2, 82% grade 1 or 2 and 66% had no nodal involvement. The median time to best response was found to be 25 months (range, 4-112 months) and the median progression-free survival through first-line PET was found to be 57 months (range, 8-155 months). Compared to tumor diameter at diagnosis, 34% had complete response, 29% had partial response, 25% had stable disease and 13% progressive disease. Of the complete responders, 100% had an Allred score of 8 for the ER and 47% had Allred score of 8 for the PR. For patients on first-line PET, objective response rate was 63%, 5-year overall survival (OS) was 63% and 10-year OS was 24%. Conclusions: PET can be associated with good tumor response and survival outcomes in patients with HR+ EBC. This study confirms PET to be a viable alternative in a subset of patients for whom non-operative management is preferred.

LBA2023 Background: Median survival for patients with glioblastoma is less than a year. Standard treatment comprises surgical debulking if feasible followed by temozolomide (TMZ) chemoradiotherapy. The objective of this clinical trial is to evaluate whether the addition of the CTLA-4 immune checkpoint inhibitor ipilimumab (IPI) improves survival. Methods: Ipi-Glio is an academic phase II, open label, stratified randomised multicentre study of IPI + TMZ (Arm A) vs TMZ alone (Arm B), after surgery and radical radiotherapy with concomitant temozolomide in patients with recently diagnosed de-novo glioblastoma. Following completion of chemoRT, patients were randomised 2:1 Arm A:B, with stratification to extent of surgery and MGMT promotor methylation. IPI 3mg/kg was administered q3/52 for 4 cycles, and TMZ 150-200mg/m2 days 1-5 q4/52 for 6 cycles. Primary outcome was overall survival (OS), treatment difference reported as hazard ratio (HR) with 60% confidence intervals (CI) and OS at 18 months. Secondary outcomes were progression-free Survival (PFS) and safety. Results: 119 patients were randomly assigned, 79 to Arm A and 40 to Arm B, at seven centres in the UK between Jan 2019 and April 2021. Patient characteristics (Arm A vs B): median Age 53 vs 48 years; male sex 70% vs 65%; ECOG PS0 70 vs 70%, PS1 30 vs 30%; MGMT promotor methylation 39% vs 40%; IDH mutation 11% vs 10%; surgical gross total resection 61% vs 60%. PFS (Arm A vs B): median PFS 10.9 months (m) vs 12.5mo, HR 1.252 (60%CI 1.01-1.54, p=0.369); 18m PFS 22% (60%CI 17-27%) vs 43% (34-51%). Overall Survival (Arm A vs B): median OS 22.7 vs 26.4 months, HR 1.223 (60% CI 0.986-1.516, p=0.431); 18 month OS 53% (60%CI 48-58%) vs 64% (56-70%). Adverse events (AE) reported by CTCAE grade (Arm A vs B): total reported AEs 1058 vs 329; no. of reported AEs per patient: mean 13.5 (SD 10.1) vs mean 8.2 (SD 7.3). Conclusions: No improvement in PFS or OS was observed with the addition of ipilimumab to temozolomide. This study does not support further investigation of this regimen in this setting. Clinical trial information: ISRCTN84434175 .

A number of imaging modalities are showing promise as predictive and prognostic biomarkers in advanced renal cell carcinoma. This review discusses progress to date in this exciting area and identifies areas of future promise.

e15608 Background: Treatment toxicity may be influenced by heterogeneity in body composition. Muscle wasting in mRCC patients treated with sorafenib is associated with increased risk of toxicity (Antoun et al, 2010). We used CT analysis to investigate changes in adipose tissue and skeletal muscle in a large cohort of mRCC patients treated with a number of targeted agents and determined whether body composition was associated with treatment toxicity. Methods: A retrospective analysis of between 2-7 sequential CT scans of 112 mRCC patients was conducted. Each patient received between 1-4 courses of therapy. In total 191 treatment episodes within this population were included; 113 courses of VEGF TKIs, 22 courses of mTOR inhibitors, 36 courses of immunotherapy and 20 episodes where no treatment was given. A validated method, using L3 as a lumbar vertebral landmark, was used to measure lumbar skeletal muscle area (cm3) and adipose tissue volume (cm3). Appendicular Skeletal Muscle Index (ASMI) was calculated to determine prevalence of sarcopenia within the cohort; sarcopenia was defined as ASMI <7.26kg/m2 for males and <5.45kg/m2for females. Toxicity was assessed by Common Toxicity Criteria (CTC) scores documented in medical records. The cohort was divided into body mass index (BMI) quartiles. Results: Of the 112 participants, 74.1% of the group had a BMI >25 at their first scan. Mean weight change between first and last scan was -3.89kg (SD: ±9.09). 20.5% of the cohort were sarcopenic at baseline, increasing to 38.4% at final scan. Sarcopenia was independent of weight change and was associated with increased frequency of severe (CTC grade > 2) treatment toxicity (Pearson Chi Square Value: 12.82; p= 0.001). This effect persisted after adjusting for BMI quartile (odds ratio = 5.04; p=0.004). Changes in bone composition and correlation of body composition with clinical outcome will also be reported. Conclusions: Sarcopenia is common in mRCC patients and is associated with a significantly increased risk of severe treatment toxicity when receiving targeted agents. Sarcopenia was seen across all BMI quartiles and was not associated with weight change.

PURPOSE To assess changes in tumor computed tomographic (CT) texture after two cycles of treatment with tyrosine kinase inhibitors (TKIs) and to determine if tumor texture correlates with measured time to progression in patients with metastatic renal cell cancer who received TKIs. MATERIALS AND METHODS A waiver of institutional review board approval was obtained for this retrospective analysis. Contrast material-enhanced CT texture parameters were assessed in 39 patients with metastatic renal cell cancer who received a TKI. A total of 87 metastases were analyzed at baseline and after two treatment cycles. Changes in tumor entropy and uniformity were derived with a software algorithm that selectively filters and extracts texture at different scales (fine to coarse detail: 1.0-2.5) and were recorded. Response assessment was also obtained by using response evaluation criteria in solid tumors (RECIST), as well as Choi and modified Choi criteria. The correlation of texture parameters and standard criteria with measured time to progression was assessed by using Kaplan-Meier analysis and a Cox regression model. Statistical significance was set at 5%. RESULTS Tumor entropy decreased by 3%-45% and uniformity increased by 5%-21% for the different scale values after administration of a TKI. With a threshold change of -2% or less for uniformity at a coarse scale value of 2.5, Kaplan-Meier curves of the proportion of patients without disease progression were significantly different and better than those for standard response assessment (P = .008 vs P = .267, P = .053, and P = .042 for RECIST, Choi, and modified Choi criteria, respectively). Cox regression analysis showed that texture uniformity was an independent predictor of time to progression (odds ratio, 4.02; 95% confidence interval: 1.52, 10.65; P = .005). CONCLUSION CT texture analysis reflecting tumor heterogeneity is an independent factor associated with time to progression and has potential as a predictive imaging biomarker of response of metastatic renal cancer to targeted therapy.

BACKGROUND:Response assessment is critical in evaluating effectiveness of anticancer treatment. Tyrosine kinase inhibitors (TKIs) in renal cell carcinoma (RCC) are associated with significant clinical benefit but may not result in significant tumor size reduction. Thus standard size-based response assessment with RECIST is insensitive, resulting in low response rates which do not reflect disease control measured by time to progression. We compared the use of combined size and density response criteria with standard size based criteria in metastatic RCC patients treated with TKI's. RESULTS:Partial response (PR) and stable disease (SD) defined by modified criteria successfully identified patients with a long TTP (448 days) or short TTP (89 days) respectively (p = 0.002). Neither RECIST nor standard Choi criteria successfully discriminated between patients having a short or long clinical benefit. PATIENTS AND METHODS:CT scans from 32 patients with metastatic RCC treated with either sunitinib (18) or cediranib (14) were assessed. Twelve patients were excluded from the analysis as ten had non-contrast enhanced scans due to renal impairment and two stopped treatment due to toxicity. Scans from 20 evaluable patients at baseline and 12 w on treatment were assessed using RECIST, Choi and modified criteria in which both a 10% decrease in size and 15% decrease in density were required to define a partial response (PR). Response assessment performed using each of the three methods was compared with time to disease progression (TTP) defined by RECIST using Kaplan-Meier statistics and Log-rank test with significance at 5%. CONCLUSION:A combined reduction in both size and arterial phase density of RCC metastases treated with TKIs correlates with TTP. RECIST and standard Choi criteria appear inferior.