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Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). Patients and methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. Results: A total of 675 patients were included; BMI was >25 kg/m2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI >25 kg/m2 versus those with BMI ≤25 kg/m2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio >4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P=.044). In the BMI ≤25 kg/m2 subgroup, significant differences were found between patients with NLR >4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO+IO versus IO+TKIs combinations (64% vs. 83%, P = .002). Conclusion: Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.

Immune checkpoint inhibitors (ICIs) represent the standard of care as first- or second-line treatment in patients with renal cell carcinoma (RCC). Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and are known to affect gut microbiota, which is gaining interest in its association with outcomes for patients on ICIs.The aim of this study was to evaluate the impact of PPIs on outcomes in RCC patients receiving immunotherapy.We retrospectively collected data from patients with metastatic RCC who received the combination of ipilimumab and nivolumab for first-line treatment (Cohort 1) or single-agent nivolumab for second-line or third-line treatment (Cohort 2) from five international centers with expertise in the treatment of RCC. Data about clinicopathological characteristics, PPI use, and outcome on ICIs were collected. Endpoints of the study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).Two hundred and eighteen patients (71% male, median age 61 years) were included in the analysis, 62 in Cohort 1 (including 25 patients receiving PPIs) and 156 in Cohort 2 (including 88 patients receiving PPIs), and were followed up for a median of 42 months. In Cohort 1, no difference was observed in ORR (48% vs 57%; p = 0.203), PFS (12.2 vs 8.5 months; p = 0.928), or OS (not reached [NR] vs 27.3 months; p = 0.84). In Cohort 2, no difference was observed in ORR (32% vs 28%; p = 0.538), PFS (6.7 vs 9.0 months; p = 0.799), or OS (16.0 vs 26.0 months; p = 0.324).In patients with RCC, concomitant PPI use did not seem to affect survival outcomes on ICIs, either as combination therapy or monotherapy.

Background Renal medullary carcinoma (RMC) is a very rare, aggressive neoplasm occurring almost exclusively in adolescents and young adults with sickle cell trait. Given the rare nature of this tumor, accounting for less than 0.5% of all renal carcinomas, most of the published data on therapies is from case reports and small case series, and current treatments are insufficient, with most patients succumbing to their disease in months. We report our experience with a cytotoxic chemotherapy regimen consisting of platinum-based therapy, doxorubicin, and bortezomib. Methods Three patients with metastatic RMC at a single institution were treated off-label with a perioperative chemotherapy regimen for 4 cycles of 2 alternating regimens: regimen A consisting of cisplatin, doxorubicin, and bortezomib; regimen B consisting of carboplatin, paclitaxel, and gemcitabine. A radical nephrectomy was performed on all patients. Surveillance imaging was performed on all patients to assess response and disease burden. Patients received up to 12 months of maintenance therapy with everolimus. Results Three African American patients - 2 males and 1 female aged 14, 28, and 31 – with sickle cell trait and metastatic disease were treated with this regimen. The median follow-up was 18 months. All had resection of the primary tumor – 2 patients after receiving neoadjuvant therapy, and one patient underwent resection prior to referral. All 3 patients achieved complete responses based on imaging, 2 of which lasted for 12 months, and another is still in remission over 7 years after diagnosis. Conclusions This regimen of alternating cycles of platinum-based chemotherapy with bortezomib appeared to be active against RMC and was generally well-tolerated. Given the extremely rare nature of this disease and dismal prognosis, new treatment modalities should be pursued, and whenever possible, patients should be enrolled in a clinical trial. We propose that a multiinstitution clinical trial of this regiment may be warranted.

Background: Renal cell carcinoma with sarcomatoid differentiation is a highly aggressive form of kidney cancer. Objective: We aimed to analyze the outcomes of patients treated with cabozantinib for metastatic renal cell carcinoma with sarcomatoid features. Methods: We retrospectively collected data from 16 worldwide centers. Overall survival and progression-free survival were analyzed using Kaplan–Meier curves. Cox proportional models were used for univariate and multivariate analyses. Results: We collected data from 66 patients with metastatic sarcomatoid renal cell carcinoma receiving cabozantinib as second-line (51%) or third-line (49%) therapy. The median progression-free survival from the start of cabozantinib was 7.59 months (95% confidence interval [CI] 5.75−17.49) and was longer in male patients (8.81 vs 5.95 months, p = 0.042) and in patients without bone metastases (7.59 vs 5.11 months, p = 0.010); the median overall survival was 9.11 months (95% CI 7.13−23.80). At the multivariate analysis, female sex (hazard ratio = 1.81; 95% CI 1.02−3.37,p = 0.046), bone metastases (hazard ratio = 2.62; 95% CI 1.34−5.10, p = 0.005), and International Metastatic Renal Cell Carcinoma Database Consortium criteria (hazard ratio = 3.04; 95% CI 1.54−5.99, p = 0.001) were significant predictors of worse overall survival. Conclusions: Our data show that cabozantinib is active in pretreated patients with sarcomatoid renal cell carcinoma. Biomarkers are needed in this field to select patients for multi-kinase inhibitors or other options.

Background Drug-drug interactions are a major concern in oncology and may potentially affect the outcome of patients with cancer. Objective In this study, we aimed to determine whether the concomitant use of statins, metformin, or proton pump inhibitors affects survival in patients with metastatic renal cell carcinoma treated with first-line combination therapies. Methods Medical records of patients with documented metastatic renal cell carcinoma between January 2016 and November 2021 were reviewed at 17 participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. Patients were assessed for overall survival, progression-free survival, and overall clinical benefit. Univariate and multivariate analyses were conducted to explore the association of variables of interest with overall survival and progression-free survival. Results A total of 304 patients receiving dual immunotherapy (51%) or immunotherapy/vascular endothelial growth factor-tyrosine kinase inhibitor (49%) combinations were eligible for inclusion in this retrospective study. Statin use was a significant prognostic factor for longer overall survival in a univariate analysis (hazard ratio 0.48, 95% confidence interval 0.26-0.87; p = 0.016) and a multivariate analysis (hazard ratio 0.48, 95% confidence interval 0.31-0.74; p < 0.001) and was significantly associated with an overall clinical benefit (83% in statin users vs 71% in non-users; p = 0.045). Otherwise, the use of metformin or proton pump inhibitors did not affect the outcome of these patients. Conclusions Our study suggests a prognostic impact of statin use in patients receiving first-line immuno-oncology combinations. The mechanism of this interaction warrants further elucidation.

Background: Statins are widely used in an ageing population, including subjects with solid malignancies. However, no conclusive evidence is currently available on their potential influence on patients' outcome. We aimed to assess whether statin exposure affects the survival of patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.Patients and methods: Medical records of patients with documented mRCC treated with second- or third-line nivolumab were reviewed at ten institutions from Italy, Spain and the USA. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit. Univariate and multivariate analyses were used to explore the association of variables of interest with survival.Results: A total of 219 patients with mRCC receiving nivolumab between January 2016 and September 2021 were eligible for inclusion in this study; 59 (27%) were statin users. The median OS (34.4 versus 18.6 months, p = 0.017) and PFS (11.7 versus 4.6 months, p = 0.013) resulted apparently longer in statin users. Stratified by age, longer median OS and PFS were associated with statin exposure in both patients aged >= 70 y (median OS: 21.4 versus 10.1 months, p = 0.047; median PFS: 16.4 versus 4.6 months, p = 0.022) and

Introduction The incidence of kidney cancer is increasing; it could be counteracted with new ways to predict and detect it. We aimed to implement an artificial neural network in order to predict new cases of renal-cell carcinoma (RCC) in the population using population rate, obesity, smoking incidence, uncontrolled hypertension, and life expectancy data in the United States. Patients and Methods Statistics were collected on US population numbers, life expectancy, obesity, smoking, and hypertension. We used MATLAB R2018 (MathWorks) software to implement an artificial neural network. Data were repeatedly and randomly divided into training (70%) and validation (30%) subsets. Results The number of new RCC cases will grow from 44,400 (2020) to 55,400 (2050), an increase of +24.7%. Our data show that preventing hypertension would have the greatest impact on reduction of the incidence, estimated at −775 and −575 cases per year in 2020 and in 2030, respectively. The prevention of obesity and smoking would have a more limited impact, estimated at −64 and −180 cases per year in 2020 and in 2030, respectively, for obesity, and −173 and −21 cases per year in 2020 and in 2030, respectively, for smoking. Conclusions Our predictions underline the need for accurate studies on RCC-related risk factors to reduce the incidence.

Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active malignancies, and thus data on the safety, tolerability and efficacy of the vaccines in patients with cancer are currently limited. Given the risk posed by the COVID-19 pandemic, decisions regarding the use of vaccines against COVID-19 in patients participating in trials of investigational anticancer therapies need to be addressed promptly. Patients should not have to choose between enrolling on oncology clinical trials and receiving a COVID-19 vaccine. Clinical trial sponsors, investigators and treating physicians need operational guidance on COVID-19 vaccination for patients with cancer who are currently enrolled or might seek to enrol in clinical trials. Considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. Herein, we provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials. In our perspective, continued quality oncological care requires that patients with cancer, including those involved in trials, be prioritized for COVID-19 vaccination, which should not affect trial eligibility., Patients with cancer have a high risk of morbidity and mortality from COVID-19. The rapid development of COVID-19 vaccines has provided new hope of mitigating the disease. Herein, the COVID19 and Cancer Clinical Trials Working Group calls for prioritization of patients with cancer, importantly including those participating in oncology clinical trials, for COVID-19 vaccination. The authors also provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials.

Background: Tyrosine-kinase inhibitors (TKIs) still represent a first-line option for selected patients with metastatic Renal Cell Carcinoma (mRCC). We aimed to compare the real-world efficacy of nivolumab or cabozantinib as second-line therapy in specific mRCC subpopulations. Patients and Methods: We retrospectively collected data from 11 centers from Italy, Spain and US. Overall Survival (OS) and Progression-Free Survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses. Results: We collected data from 343 patients with mRCC, 123 (36%) treated with cabozantinib and 220 (64%) with nivolumab. The median OS resulted longer, but not statistically significant, with nivolumab in patients aged >70 years (21.4 vs. 15.4 months, P = .746), treated with first-line pazopanib (26.8 vs. 11.6 months, P = .450), or with good (47.0 vs. 15.5 months, P = .285) or intermediate-risk criteria (14.4 vs. 11.0 months, P = .357), while it was longer, but even not statistically significant, for cabozantinib in patients who received previous sunitinib (25.7 vs. 21.7 months, P = .638) or with bone metastases (28.4 vs. 24.4 months, P = .871). The median PFS was significantly longer with cabozantinib in patients with clear cell histology (7.8 vs. 5.4 months, P = .026) and in patients with good risk features (12.3 vs. 5.7 months, P = .022). Conclusions: Nivolumab and cabozantinib resulted active in mRCC patients, showing distinct results when stratified into clinico-pathological features.

Background: Clinical research studies often integrate precision medicine technologies and techniques, offering novel treatment opportunities for patients but also posing significant challenges for regulatory authorities and local institutional review boards (IRBs) as they attempt to protect patient safety and privacy. Methods: We review the basics of precision medicine and discuss how IRBs are addressing new challenges associated with the era of precision medicine. Results: Precision medicine trials rely on genomic testing for inclusion criteria and investigational drug therapy choices. The vast amounts of complex information that can be obtained from basic genetic sequencing tests must be stored, analyzed, and interpreted, creating challenges for clinicians, researchers, and regulatory staff who are concerned with complex ethical, security, and legal issues surrounding patients’ personal genetic data in the digital age. All members of the IRB face a rapidly changing environment. The traditional areas of primary concern, such as patient privacy, terminology, and financial benefits, have been joined by issues associated with precision medicine, such as accelerated US Food and Drug Administration drug approval, multiple informed consent form modifications, increasing length and complexity of informed consent forms, and participant genetic privacy. The challenge to the IRB is to remain focused on the prior areas of significance while also adapting the evaluation process to the novel science of precision medicine. Conclusion: In this era of exponentially increasing big data and easy-to-access genetic sequencing data, IRBs will be tasked with adapting their processes and adjusting to the new technology and its corresponding complexities. Such adaptation has always been required of IRBs, but now it will need to occur rapidly as technology and data analysis capabilities accelerate.

The primary endpoint of MOUSEION-01 was to assess overall survival (OS) in male and female patients receiving immune checkpoint inhibitors versus control treatments, calculating the pooled OS Hazard Ratio (HR) and 95 % Confidence Interval (CI) in both groups. 37 randomized phase III studies and 22646 patients (16382 men and 6264 women) were included. In patients treated with immunotherapy (as monotherapy or in combination with other agents), the pooled OS HR was 0.78 (0.75-0.82) and 0.77 (95 % CI, 0.72-0.83) in male and female subjects, respectively. The pooled HR for OS in male patients treated with single-agent immunotherapy versus control was 0.77 (95 % CI, 0.70-0.85), while this benefit was smaller in female patients (HR, 0.81; 95 % CI, 0.73-0.9). Our findings highlight that high-quality trials accounting for potential confounders are needed before being able to suggest a real effect of the patient's gender on immune checkpoint inhibitors efficacy in different settings.

To identify the optimum response criteria for first-line targeted pazopanib therapy in patients with mRCC using solid tumor response criteria and clinical risk factors. Pre- and post-treatment CTs of patients (n = 43) with mRCC treated with first-line pazopanib therapy were analyzed retrospectively. Treatment response was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Choi, modified Choi (mChoi), revised Choi (rChoi), MASS (Morphology, Attenuation, Size, and Structure), 10% threshold criteria, and subjective assessment. Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium clinical risk factors were also used to define response groups. Response evaluations were correlated with overall survival (OS) and progression-free survival (PFS) using log-rank test. Patients with partial response (PR) by mChoi and rChoi had longer OS than those with stable disease (SD) (P

Background: A subset of patients with metastatic renal cell carcinoma (mRCC), deemed as primary refractory, shows progressive disease as the best response to first-line therapy even when treated with novel immune-based combos. Objective: We aimed to assess the outcome of patients treated with second-line cabozantinib for mRCC primary refractory to first-line therapy defined as Response Evaluation Criteria in Solid Tumors (RECIST) progression in the computed tomography scan as the best response to the upfront treatment. Design, setting, and participants: We retrospectively collected data from 11 worldwide centers. Outcome measurements and statistical analysis: Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses. Results and limitations: We collected data from 108 patients with mRCC primary refractory to pembrolizumab plus axitinib (17%), nivolumab plus ipilimumab (36%), or tyrosine kinase inhibitors (TKIs; 31% sunitinib and 16% pazopanib). The median OS with cabozantinib was 9.11 mo, and it was 8.84 and 9.11 mo in patients primary refractory to immunocombinations and TKIs, respectively (p = 0.952). A significant difference was found between patients primary refractory to pembrolizumab plus axitinib (OS not reached) and those primary refractory to nivolumab plus ipilimumab (median OS 8.12 mo, p = 0.024). The median PFS with cabozantinib was 7.30 mo, without significant differences between patients primary refractory to immunocombinations and those primary refractory to TKIs (6.90 vs 7.59 mo, p = 0.435) or between patients primary refractory to pembrolizumab plus axitinib and those primary refractory to nivolumab plus ipilimumab (7.92 and 6.02, p = 0.509). Investigator-assessed overall response rates were 21% and 12% in patients primary refractory to first-line immunocombinations and TKIs, respectively, with a clinical benefit of 48% in the overall population. Conclusions: Our data show that cabozantinib is active in primary refractory mRCC patients regardless of which treatment is received as first-line therapy. Systemic options and prognosis of primary refractory patients with mRCC, particularly those treated with novel immune-based combos, are among the major challenges that we need to face in this field. Patient summary: Patients primary refractory to first-line therapy are characterized by a poor prognosis. Herein, we aimed to assess the outcome of patients treated with second-line cabozantinib for metastatic renal cell carcinoma (mRCC) primary refractory to first-line therapy. Our results suggest that cabozantinib is active in primary refractory mRCC patients.

For the second year in a row, the annual meeting of the American Society of Clinical Oncology (ASCO) was held virtually due to the ongoing COVID-19 pandemic. Nonetheless, the meeting was hailed as a great success and brought much practice changing data in the field of genitourinary medical oncology, including kidney cancer.

BackgroundCorticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy.MethodsWe retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs ResultsWe identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, pConclusionOur results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

Cancer in Louisiana is a significant problem, with both incidence and death rates from the disease far surpassing national averages.1 In fact, the problem is so pervasive that the region between Ba...

Objective: To investigate whether patients requiring dialysis are a higher risk surgical population and would experience more perioperative adverse events even when undergoing a perceived less invasive operation as a laparoscopic radical nephrectomy (LRN). LRN is generally a well-tolerated surgical procedure with minimal morbidity and mortality. Prior to transplantation, dialysis patients will often have to undergo a LRN to remove a native kidney with a suspicious mass. Materials and Methods: Patients in the American College of Surgeons National Surgical Quality Improvement Program who underwent a LRN between 2011 and 2016 were included. Patients were stratified by the need for preoperative dialysis 2 weeks prior to surgery, and perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between the need for preoperative dialysis and perioperative risk. Results: There were 8315 patients included in this analysis of which 445 (5.4%) patients required preoperative dialysis. Patients who required preoperative dialysis had more minor (P

Introduction Adenoid cystic carcinoma (ACC) is a rare malignant neoplasm within the secretory glands of the head and neck. Clinical findings include a lump on the palate, tongue, or bottom of the mouth. Because symptoms can be mild, patients go for long periods of time without investigation. ACC is diagnosed using histology. Treatment is by surgical resection because there is no effective chemotherapy. Radiation can be effective adjuvant therapy, and proton therapy and stereotactic irradiation can be used for those who are ineligible for surgery. Immunotherapy has clinical activity for those with metastatic head and neck cancers who progress on proton therapy. This case reviews the use of immunotherapy in a patient with ACC. Case presentation A man in his 20s presented with a 6-month history of nasal congestion, epistaxis, and sinus tenderness. Noncontrast computed tomography of the sinuses revealed a mass of the lateral wall of the nasal cavity, lateral wall of the maxillary sinus, and pterygoid plates. Positron emission tomography confirmed metastatic disease in the right iliac crest and right cervical lymph node; biopsy of the nasopharynx confirmed ACC. The patient received proton therapy and intensity-modulated radiotherapy and completed 2 Phase 1 trails but continued to have progressive disease. The patient started nivolumab and died 12 weeks later. Conclusion The patient recently received proton therapy, intensity-modulated radiotherapy, and completed 2 Phase 1 trials but continued to have progressive disease.

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan&ndash, Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI &ge, 25 (9.9 vs. 7.6 months, p &lt, 0.001). The median OS was higher in the BMI &ge, 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI &ge, 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI &ge, 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.

Background There are increasing numbers of immune checkpoint inhibitors (CPI) targeting the PD-1/PDL-1 and CTLA-4 pathways, which are approved in a wide variety of tumor types. A case series has previously described the sequential use of first line CPI, followed by second line CPI in renal cell carcinoma and melanoma patients, and both patient population had progressive disease. There is still a lack of data on the safety and efficacy of challenging a patient who has previously progressed on a CPI with a different class of CPI, in other tumor types. Methods We retrospectively collected data from patients treated with a CPI, who were subsequently challenged with another CPI, at a single institution. Exclusion criteria included patients with renal cell carcinoma and melanoma. Patient characteristics, immune-related adverse effects (irAEs), cancer type, tumor proportion score if available, treatment type, treatment response/progression per RECIST v1.1, and survival data were collected. Results We identified 11 patients with various pathologies who received sequential CPI after progressing on first line CPI (table 1). Cancer types included non-small cell lung cancer (n=5), head and neck cancer (n=2), urothelial carcinoma (n=1), Merkel cell carcinoma (n=1), poorly differentiated carcinoma (n=1), and hepatocellular carcinoma (n=1). The tumor proportion score was available in 6 patients. Out of these patients, all were metastatic at the time of second line CPI. First line CPIs were all PD(L)-1 inhibitors, second line CPIs were all PD(L)-1 inhibitors except for one patient who received a CTLA-4 inhibitor in combination with a PD-1 inhibitor. Out of these patients, 3 patients who were trialed with second line CPI had stable disease, 5 patients had progression of disease, 1 patient had an irAE leading to discontinuation of CPI, and 2 patients died from adverse events unrelated to CPI. Out of 3 patients with stable disease on second line CPI, 2 patients had stable disease for over 2 years, and 1 patient has had stable disease for over 1 year. Conclusions Despite concerns that sequential immunotherapy may not be efficacious, 3 out of 11 patients did significantly benefit with the long-term stable disease. We need further large-scale prospective studies and research to know more about tumor characteristics, the mechanism of resistance in immuno-oncology to help us identify patients who would benefit from sequential immunotherapy.

BACKGROUND: This is the largest and only multivariate study evaluating the difference in mortality from coronavirus disease 2019 (COVID-19) between patients with cancer and patients without cancer in the United States. The objective was to assess COVID-19 mortality rates in patients with cancer versus patients without cancer and uncover possible statistically significant characteristics contributing to mortality. METHODS: This retrospective study analyzed patients with cancer and patients without cancer who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 1 through April 30, 2020. This was a multicenter study in the state of Louisiana throughout the Ochsner Health System in both tertiary and nontertiary centers. Patients older than 18 years were eligible. Three hundred twelve patients with cancer were compared with 4833 patients without cancer. RESULTS: Mortality was found to be higher in the cancer group. Patients of advanced age with cancer had a significant increase in mortality (odds ratio [OR], 5.96; P < .001). Other significant risk factors for increased mortality were male sex (OR, 2.15), a history of chronic kidney disease (OR, 3.84), and obesity (OR, 1.30). In hospitalized patients with cancer, adverse vital signs on admission, decreased absolute lymphocyte counts, thrombocytopenia, elevated creatinine, lactic acidosis, and elevated procalcitonin all seemed to increase the risk of death. Among patients with cancer, active or progressive disease (P < .001) and recent therapy (OR, 2.34; 95% confidence interval, 1.08-5.08) were shown to increase mortality. CONCLUSIONS: Patients with cancer have increased mortality in the setting of infection with SARS-CoV-2 in comparison with patients without cancer. Patients with cancer who are 65 years of age or older and those with certain comorbidities have the greatest risk of death. Recent cancer-directed therapy and disease status also seem to play roles in mortality. LAY SUMMARY: This is the largest study of patients with cancer versus patients without cancer to date and is the first multivariate analysis study comparing these 2 patient populations. This study confirms the hypothesis that patients with cancer are at increased risk for mortality and that there are multiple characteristics posing the potential to risk-stratify these patients in the setting of a future outbreak.

To examine the rates of adverse surgical outcomes in patients undergoing cytoreductive nephrectomy (CN) compared to patients undergoing radical nephrectomy in the nonmetastatic setting using a large administrative database.Patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) who underwent a radical nephrectomy between 2011 and 2016 were included. Patients were stratified by the preoperative variable of presence or absence of metastatic cancer. Perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between patients with metastatic cancer and perioperative morbidity and 30-day mortality.There were 15,869 total patients included in this analysis of whom 1322 (8%) patients had metastatic cancer. Of the entire cohort, the majority of patients were over 60 years old (58%) and 9621 (61%) were male. Seventy-three of the patients were Caucasian. Patients with metastatic cancer had more minor (P.01) and major (P.01) complications, a higher rate of reoperation (P.01), and a higher rate of unplanned readmissions (P.01). Finally, the cohort with metastatic cancer had a higher rate of postoperative 30-day mortality (P.01) than patients without metastatic cancer.Patients undergoing a CN have significantly worse perioperative outcomes than patients undergoing a radical nephrectomy without evidence of metastases. Careful surgical risk stratification and appropriate patient counseling should be undertaken when selecting candidates for CN.

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan&ndash, Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51&ndash, 10.88) and 11.57 months (95% CI 10.90&ndash, not reached (NR)) as second-line and 11.38 months (95% CI 5.79&ndash, NR) and NR (95% CI 11.51&ndash, NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib&ndash, nivolumab and 25.64 months and NR with nivolumab&ndash, cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39, 95% CI 1.24&ndash, 4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04&ndash, 2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33, 95%CI, 1.16&ndash, 4.69, p = 0.018) and Hb levels (HR = 3.12, 95%CI 1.18&ndash, 8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72, 95%CI 1.04&ndash, 7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

// Jessie Gills 1, * , Ravan Moret 2, * , Xin Zhang 2 , John Nelson 1 , Grace Maresh 2 , Linh Hellmers 2 , Daniel Canter 1 , M’Liss Hudson 1, 6 , Shams Halat 3 , Marc Matrana 4 , Michael P. Marino 5 , Jakob Reiser 5 , Maureen Shuh 2 , Eric Laborde 1 , Maria Latsis 1 , Sunil Talwar 1 , Stephen Bardot 1 and Li Li 2 1 Department of Urology, Ochsner Clinic Foundation, New Orleans, LA, USA 2 Institution of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, USA 3 Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA, USA 4 Department of Hematology and Oncology, Ochsner Clinic Foundation, New Orleans, LA, USA 5 Division of Cellular and Gene Therapies, The Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA 6 Current address: Memorial Urology Associates, Houston, TX, USA * These authors contributed equally to this work Correspondence to: Stephen Bardot, email: sbardot@ochsner.org Li Li, email: lli@ochsner.org Keywords: patient-derived orthotopic xenograft; high-grade/muscle invasive urothelial cell carcinoma; lymph node stromal cells Received: June 26, 2018 Accepted: August 10, 2018 Published: August 24, 2018 ABSTRACT High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph node stromal cells (HK cells). Mice were monitored weekly with bioluminescence imaging to assess tumor growth and metastasis. Primary tumors and organs were harvested for bioluminescence imaging, weight, and formalin-fixed for hematoxylin and eosin and immunohistochemistry staining. In this patient-derived orthotopic xenograft model, xenograft tumors showed better implantation rates than currently reported using other models. Xenograft tumors histologically resembled pre-implanted primary specimens from patients, presenting muscle-invasive growth patterns. In the presence of HK cells, tumor formation, tumor angiogenesis, and distant organ metastasis were significantly enhanced in both UM-UC-3 cells and patient-derived specimens. Thus, we established a unique, reproducible patient-derived orthotopic xenograft model using human high-grade urothelial cell carcinoma cells and lymph node stromal cells. It allows for investigating the mechanism involved in tumor formation and metastasis, and therefore it is useful for future testing the optimal sequence of conventional drugs or the efficacy of novel therapeutic drugs.

Background: Immune checkpoint inhibitors produce prolonged responses in select non-small cell lung cancer (NSCLC) patients, however the identification of patients most likely to benefit is difficult. Pretreatment derived neutrophil-to-lymphocyte ratio (dNLR) is an easily calculated marker available in routine clinical care that has shown prognostic value in many cancer treatment settings, but its association with survival in NSCLC patients treated with immune-checkpoint inhibitors is less understood. Patients and Methods: We retrospectively reviewed 72 NSCLC patients receiving either nivolumab or pembrolizumab between 3/1/15 and 3/1/17 with a median follow-up time of 5.1 months. Patients were compared using Cox proportional hazards models to detect an association between pretreatment dNLR 3 vs ≥3 on overall survival (OS), progression-free survival (PFS) and overall response rate. Results: Median age was 65 (range: 41 - 86), 65% were male, 40% received ≥ 2 prior systemic therapies and 14% had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2. Pretreatment dNLR ≥ 3 was independently associated with shortened OS (median 3.6 vs 8.5 months; HR: 5.4; 95% CI: 2.0 - 14.6; p = 0.001) and PFS (median 2.1 vs 3.4; HR: 2.3; 95% CI: 1.1 - 4.8; p = 0.027). Conclusion: Pretreatment dNLR ≥ 3 was independently associated with inferior survival in NSCLC treated with immune checkpoint inhibitors in routine practice. Prospective verification of this marker is warranted as it could serve as an inexpensive and widely-available marker for identifying NSCLC patients most likely to benefit from PD-1 inhibitors.

The urachus is a fibrotic remnant of the allantois, a canal that collects liquid waste and exchanges gases from the fetal bladder with the umbilical cord. Urachal cancer is a rare and aggressive cancer that often presents as adenocarcinoma at the dome of the bladder.If urachal carcinoma is found early and confined to the urachus, cystectomy with en bloc resection of the urachal ligament and umbilicus can be curative. For unoperable patients, chemotherapy has a low rate of efficacy.In this case we explore the effects of Gem-FLiP (gemcitabine, 5-fluorouracil, leucovorin, and cisplatin) in the treatment of urachal carcinoma, a regimen that is undergoing clinical trials. A 76-year-old man with a long history of genitourinary disease presented with gross painless hematuria. A flexible cystoscopy showed a sessile tumor at the dome of the bladder. A computed tomography (CT) urogram of the abdomen and pelvis confirmed a mass at the dome of the bladder. A CT-guided biopsy revealed adenocarcinoma consistent with urachal cancer.After beginning treatment with Gem-FLiP, he developed pedal edema as well as drainage of the umbilicus. A CT scan of the abdomen and pelvis showed an anterior extension through the abdominal wall just below the umbilicus with central hypoattenuation within the mass; this represented a fistula between the bladder and umbilicus, along the tract of the urachal ligament, therefore confirming the diagnosis of urachal cancer.This case illustrates a clinical scenario in which urachal carcinoma was confirmed when the entire cancerous urachus fistulized in response to treatment with systemic chemotherapy. It is highly unusual that a response to chemotherapy confirms a diagnosis.

The purpose of this study is to compare the prognostic value of various solid tumor response criteria as well as the additive value of clinical risk factors in patients with advanced renal cell carcinoma (RCC).Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months after treatment) were reviewed for 57 patients with metastatic RCC treated with pazopanib in the salvage setting. Tumor response on the posttherapy scan was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi, modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and 10% threshold criteria. In addition, combined Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors plus imaging criteria were used to define response groups. Response evaluations using these criteria were correlated with overall survival (OS) and progression-free survival (PFS), with use of the log-rank test.Patients classified as having progressive disease (PD) on the basis of RECIST, mChoi, and MASS criteria had a significantly worse OS than patients with stable disease (SD) and partial response (PR). With the addition of MSKCC risk factors, all groups with PD defined by combined criteria had significantly worse OS. For 37 patients with no or one MSKCC risk factor, response groups defined by Choi, mChoi, MASS, and 10% threshold criteria did not differ in PFS or OS. However, among 20 patients with two to three MSKCC risk factors, those classified as having PR had longer PFS than did those with SD and had longer OS than did those with PD.For patients with advanced RCC for which prior therapies have failed, the prognostic value of various imaging-based tumor response criteria differs on the basis of the MSKCC clinical risk status.

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase I and II trials (the latter including subjects with CNS involvement) [AACR #1185, 2013; AACR #CT 129, 2019]. The primary aims of the previously reported Phase I/II DM-CHOC-PEN trials were to assess clinical response and monitor toxicities/safety and verify the maximum tolerated doses (MTD) for IV administered DM-CHOC-PEN (IND 68,876) to subjects with cancer. We report here the responses and toxicities seen in subjects with NSCLC involving the CNS that lacked genetic rearrangements, tumor targets and/or had failed standard therapies. Subjects & Methods: DM-CHOC-PEN was administered to adults (> 18 y/o) as a 3-hr IV infusion once every 21 days employing a verified 2-tiered MTD schedule: 85.8 mg/m2 for subjects with liver involvement and 98.7 mg/m2 for subjects with normal livers. Results: Fifty two (52) adult subjects with cancer have been treated to date, including16 subjects with lung cancer, of which 11 had NSCLC (adeno/large cell carcinomas) involving the CNS that lacked genetic rearrangements/no tumor targets and/or had failed standard therapies. Seven of the 11 subjects with NSCLC involving the CNS also possessed cerebellar metastases. The drug was well tolerated; the most common adverse effects were fatigue (17%), reversible liver dysfunction (9%) and nausea (11%). No neuro/psychological, hematological, cardiac or renal toxicities were observed, nor drug associated deaths. PK modeling revealed that AUCs were parallel for both the 85.8 and 98.7 mg/m2 doses employed. The Cmax for DM-CHOC-PEN and DM-PEN (4-demethylpenclomedine, a metabolite) at the MTD were 3 and 24 hours, respectively. Both DM-CHOC-PEN and DM-PEN were detected for up to 15 days post administration associated with rbc's. DM-CHOC-PEN was also detected in CNS tumor tissue obtained anatomically from five (5) subjects - in concentrations of 75-210 ng/g, 22 days to 9 mos. post-treatments. 8 subjects have responded with CR/PR (RECIST 1.1) and improved OS/QOL/PFS (Kaplan-Meier) lasting 8+ - 70+ mos. Conclusion: DM-CHOC-PEN is a bis-alkylator of DNA that is safe at the dose levels described and has produced long term objective responses with manageable toxicities in subjects with NSCLC involving the CNS lacking genetic rearrangements or tumor targets and/or had failed standard therapies. Complete data on subject responses and observed toxicities will be presented. A 3-stage mechanism is proposed for drug entry into the CNS and into NSCLC cells via reversible binding with RBC's and then associated with L-glutamine transport into cells. Supported by NCI/SBIR grants - R43/44CA132257 and NIH NIGMS 1 U54 GM104940 - the latter funds from the Louisiana Clinical and Translational Science Center, New Orleans, LA. Citation Format: Roy S. Weiner, Lee Roy Morgan, Marcus Ware, Tallat Mahmood, Craig Gordon, Manish Bhandari, Andrew Rodgers, Marc Matrana, Thomas M. Cosgriff, Philip Friedlander, Jay J. Zou. Phase II clinical trial results for 4-demethyl-4-cholesteryloxycarbonyl-penclomedine (DM-CHOC-PEN) in advanced non-small cell lung cancer (NSCLC) involving the CNS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT152.

Background Pazopanib is associated with increased progression-free survival (PFS) in clear-cell renal cell carcinoma (RCC) and has become a standard of care in this disease. The drug is used in metastatic non–clear-cell RCC, but data on outcomes in this setting are limited. Patients and Methods We conducted a retrospective data analysis of records of consecutive metastatic non–clear-cell RCC patients who received pazopanib in front-line and salvage settings between November 2009 and November 2012. Tumor response rate was assessed by a blinded radiologist using Response Evaluation Criteria in Solid Tumors version 1.1. PFS and overall survival (OS) times were estimated using Kaplan–Meier methods. Results Twenty-nine patients were identified with non–clear-cell metastatic RCC, 9 received pazopanib in the front-line setting, 20 in the salvage setting after progression of disease with other targeted therapies. Seven patients (24%) had papillary RCC, 4 (14%) had chromophobe, 5 (17%) had unclassified histopathology, and 13 (45%) had other subtypes including collecting duct, translocation Xp11.2, and various subtypes with sarcomatoid differentiation. All patients discontinued pazopanib before analysis. Median PFS was 8.1 months (95% CI, 5.7-NA [not available]) in the front-line group, and 4 months (95% CI, 2.1-9.9) in the salvage group. Median OS was 31 months (95% CI, 9.2-NA) in the front-line group, and 13.6 months (95% CI, 6.4-NA) in the salvage group. Conclusion Pazopanib showed efficacy in patients with metastatic non–clear-cell RCC in the front-line and salvage settings. Toxicity was mild to moderate and manageable. Further studies are needed to evaluate pazopanib's role in non–clear-cell RCC in terms of efficacy and safety.

INTRODUCTION AND OBJECTIVES:Renal cell carcinoma (RCC) incidence is increasing, and metastatic disease effects up to 25% of RCC patients. Additionally, RCC has varying prognoses and therapy respons...

Background: Pancreatic ductal adenocarcinomas (PDAC) exhibit a high degree of desmoplasia with extensive connective tissue growth factor (CTGF) expression and extracellular matrix production. Tumor response and potential for resection in locally advanced unresectable pancreatic cancer (LAPC) may be affected by pamrevlumab via improved antitumor effect and/or by affecting tumor margins through inhibition of CTGF overexpression. Methods: This is Phase I/II safety/efficacy study in locally advanced pancreatic patients. 37 patients were randomized 2:1 to gemcitabine/nab-paclitaxel plus pamrevlumab (Arm A, n=24) or gemcitabine/nab-paclitaxel alone (Arm B, n=13). Those who completed 6 cycles of treatment were assessed for surgical eligibility, and if eligible, underwent surgical exploration for resection. Patients who did not finish initial chemotherapy received second-line treatment as per standard of care. The study is registered at ClinicalTrials.gov, with a registry number of NCT02210559. Findings: 75% of patients in Arm A and 54% in Arm B completed 6 cycles of therapy. In Arms A and B, CA 19-9 response, as defined by ≥50% decline from baseline occurred in 65% and 42%, respectively; median decline was 93% versus 78%, respectively. Best objective RECIST response was ~30% in each treatment arm. Sixteen percent of patients were radiographically down-staged by NCCN criteria (5 in Arm A and 1 in Arm B). PET SUVmax declined by ≥30% at end of treatment in 60% of patients overall. PET normalized in 38% vs 23% of patients in Arm A vs Arm B, respectively. PET SUVmax normalization at EOT strongly correlated with eligibility for surgical exploration and resection in Arm A and B. Eligibility for surgical exploration was 71% vs 15%, (p=.0019) and resection was achieved in 33% vs 8% of patients in Arm A vs Arm B (p=0.1193), respectively. Interpretation: Pamrevlumab may be a valuable addition to gemcitabine/nab-paclitaxel neoadjuvant therapy in LAPC without added toxicity. This combination merits evaluation in a larger patient population. Trial Registration Number: The study is registered at ClinicalTrials.gov, with a registry number of NCT02210559. Funding: The study was funded by FibroGen, Inc. Declaration of Interest: VP reports other from Ipsen, other from Novocure, other from OncoMed, other from Tyme, other from Celgene, other from Lilly, other from Aduro, FR I/We declare no competing interests, JW I/We declare no competing interests, MP reports other from Genentech, other from Pfizer, other from Merck, other from Astra Zeneca, other from Medimmune, other from Celldex, personal fees and other from ARMO, personal fees and other from Celgene, other from Boston Biomedical, other from Tesaro, other from Bavarian Nordic, other from Novartis, other from BMS, other from Abbvie, other from Halozyme, other from Karyopharm, other from Bayer, other from Regeneron, personal fees from Sirtex, personal fees from Caris, personal fees from Rafael, personal fees from Eisai, personal fees from Ignyta, personal fees from Ipsen, personal fees from Merrimack, outside the submitted work, KM reports other from Agios, other from Senwah Biosciences, other from Taiho, other from Arqule, other from Astra Zeneca, other from Genentech, other from Incyte, other from Tracon Pharmaceuticals, other from Medimmune, other from Puma Biotechnology, personal fees from Astra Zeneca, personal fees from Bayer, personal fees from Celgene, personal fees from Eisai, personal fees from Exelixis, personal fees from Merrimack, personal fees from Vicus, personal feels from Ipsen, outside the submitted work, JG reports other from Genentech, other from Generon, other from GlaxoSmithKline, other from Hana Biosciences, other from Kyowa, other from Novartis, other from Odonate, other from Pfizer, other from Polynoma, other from Terapure, TL I/We declare no competing interests, MM I/We declare no competing interests, MC is employed by FibroGen, MZ is employed by FibroGen, SP is employed by FibroGen, EK is employed by FibroGen, TN is employed by FibroGen, EC is employed by Fibrogen Ethical Approval: The study was approved by individual institutional review boards at 9 US institutions and conducted according to the Declaration of Helsinki.

Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active malignancies, and thus data on the safety, tolerability and efficacy of the vaccines in patients with cancer are currently limited. Given the risk posed by the COVID-19 pandemic, decisions regarding the use of vaccines against COVID-19 in patients participating in trials of investigational anticancer therapies need to be addressed promptly. Patients should not have to choose between enrolling on oncology clinical trials and receiving a COVID-19 vaccine. Clinical trial sponsors, investigators and treating physicians need operational guidance on COVID-19 vaccination for patients with cancer who are currently enrolled or might seek to enrol in clinical trials. Considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. Herein, we provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials. In our perspective, continued quality oncological care requires that patients with cancer, including those involved in trials, be prioritized for COVID-19 vaccination, which should not affect trial eligibility.

287 Background: There are many clinical trials that demonstrate the benefits of immunotherapies and targeted therapies in patients (pts) with advanced or metastatic RCC (mRCC). Most of these studies specifically exclude many real-world pts with comorbidities such as autoimmune disease, heart failure, and hypertension. Data on treatment efficacy and adverse events in patients with a history of uncontrolled hypertension is lacking, as there have been few studies analyzing more recently approved RCC drug regimens in real-world practice. Methods: We retrospectively collected data from pts with mRCC treated with immunotherapy and/or targeted therapies. Patient characteristics, performance status, treatment type, reason for treatment discontinuation, treatment response/progression per RECIST v1.1, survival, and presence of clinical trial exclusion criteria such as hypertension, heart failure, presence of autoimmune disease, renal or liver failure, and International Metastatic RCC Database Consortium (IMDC) Risk score were collected. Results: A total of 198 pts were included. The majority of patients received Tyrosine Kinase Inhibitors (TKIs) (42.42% pazopanib (n = 84), 21.71% sunitinib (n = 43), 13.64% cabozantinib (n = 27)), whereas 10.61% were on combination of axitinib + pembrolizumab (n = 21) and 11.62% received ipilimumab + nivolumab (n = 23), and. 71.72% of patients who qualified for systemic therapy had a history of uncontrolled hypertension, whereas 28.28 % of total patients had no history of uncontrolled hypertension. The median time on first-line treatment was 5.17 months. A history of hypertension did not significantly affect Overall Survival (OS), 15.90 months median OS for those with hypertension vs 27.80 median OS for those with no hypertension (p = 0.38). Median OS for all patients was 22.80 months. There was also no difference in response rate between those with a history of hypertension vs those with no history of uncontrolled hypertension (p = 0.65) or in Progression Free Survival (PFS) (p = 0.97) Data on how many patients developed exacerbations of hypertension on therapy will be available at time of presentation. Conclusions: Uncontrolled hypertension typically excludes patients from clinical trial enrollment. We found no difference in median OS in those with a history of hypertension compared to those with normal blood pressures. Further large-scale studies are needed to further determine outcomes in patients with hypertension on systemic therapy for mRCC.

Emerging immunotherapies targeting immune checkpoints and tumor associated antigens are leading to important clinical advances and providing a new weapon in patients with prostate (PCa) and bladder cancer (BC) and, in particular, with renal cell carcinoma (RCC). The possibility to integrate these agents in the current therapeutic scenario or genitourinary tumors, both in sequential or combined approaches, relies on a more profound comprehension of the protumorigenic activity of the immune system and of the mechanisms of cancer-related immunosuppression. In this regards, neutrophils, T and B lymphocytes and tumor-associated macrophages (TAMs) are implicated in the pathogenesis, progression and development of drug resistance in genitourinary tumors. This review is an overview on the recent insights concerning the role of immune cells in this context.

3574 Background: Tissue-based h-CGP is increasingly utilized for treatment selection in patients with advanced solid tumors but has high tumor surface area [TSA] requirements (≥25mm2 for leading commercial tests). P-CGP is recommended when tissue is insufficient for H-CGP. Here we assessed the feasibility and clinical impact on actionable biomarker identification of PCR-CGP. Methods: We performed a post-hoc, non-prespecified analysis on 21,743 consecutive subjects with advanced solid tumors who sent TTS for PCR-CGP from 5/17-12/19 as part of an ongoing observational trial at > 20 U.S. health systems (NCT03061305). PCR-CGP was performed using StrataNGS, a single-site laboratory developed test assessing all CGP biomarker classes (including microsatellite instability (MSI) status and tumor mutation burden [TMB]). We predicted actionable biomarker identification rates for PCR-CGP, H-CGP and P-CGP if applied to all U.S. patients with advanced solid tumors through incorporating population incidence, biomarker frequencies, test TSA and tumor content requirements (or cfDNA detection rates), and performance characteristics. Actionable biomarkers were the 30 in 11 tumor types from the MolDX p-CGP local coverage determination (L38043), pan-tumor NTRK fusions and MSI, and TMB in lung cancer. Results: Among TTS from 21,734 patients with advanced cancer, 20,493 (94.3%) met TSA requirements for PCR-CGP (≥2mm2) vs. 9,281 (42.7%) for H-CGP. PCR-CGP reported results for 98.0% and 95.0% of patients with large (≥25mm2 TSA) and small (2-24mm2) TS, respectively, in a median of 7 business days. Compared to 1,882 orthogonal actionable biomarker results, PCR-CGP accuracy was 96.6% and 96.5% in large and small TTS, respectively. Actionable biomarker frequency was highly correlated in PCR-CGP tested large vs. small TTS (r2= 0.99), as well as in this PCR-CGP cohort vs. a MSKCC institutional pan-cancer H-CGP cohort (r2= 0.92). If applied to all U.S. patients with advanced solid tumors, PCR-CGP has significantly greater predicted actionable biomarker identification rate (88.5%) compared to P-CGP (77.0%, N-1 chi-squared test, p < 0.0001) or H-CGP (54.3%, p < 0.0001). Conclusions: Half of TTS submitted for PCR-CGP did not meet H-CGP tissue requirements. PCR-CGP is feasible for the vast majority of patients and is predicted to expand the actionable biomarker evaluable proportion of patients with advanced solid tumors compared to H-CGP or P-CGP. Clinical trial information: NCT03061305 .

e15133 Background: Steroids are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether steroids have an effect on immune checkpoint inhibitor (CPI) efficacy compared patients receiving steroids vs. no steroids. This comparison may be confounded by different rates of irAEs and a known association of irAEs with higher response rates to CPIs. There is a paucity of CPI efficacy data in relation to the total dose of concomitant steroids. Methods: We retrospectively collected data from patients treated with CPIs alone, who received steroids during their CPI treatment at a single institution. IrAEs were defined using the CTCAEv5 criteria. Response rate (RR) and progression were defined per RECIST v1.1. Kaplan Meier and Cox proportional hazard regression methods were used to estimate the survival probability and hazard ratios (HR). Results: We identified 260 patients with stage IV cancer who received steroids concurrently with CPI treatment. A total of 111 patients (42.7%) received ≥1000mg prednisone equivalence during the course of their CPI treatment, and the remaining 149 patients (57.3%) received < 1000mg PED. There was no difference in progression free survival (PFS) between the two cohorts [HR of 0.923 for < 1000 mg PED group; p = 0.6016] or in overall survival (OS) [0.854 for < 1000 mg PED group, p = 0.3308]. Median PFS for the < 1000mg group was 5.9 months (mo), vs 6.3 mo in the ≥1000mg group. Median OS for the < 1000mg group was 15.76 mo, vs 11.53 mo in the ≥1000mg group. The RR was numerically higher in the prednisone < 1000mg cohort at 29.53% vs 20.72% in the ≥1000mg cohort, however not statistically significant (p = 0.1082). Basic characteristics including sex, race, tumor type, and smoking status, were similar between the two groups. There was a statistically significant difference in BMI distribution and steroid indication (irAE indication higher in >1000 mg PED cohort than non-irAE) between the two groups. Conclusions: PFS, OS, and RR were not different between patients who received >1000mg vs. < 1000mg PED during CPI therapy. These data suggest that even high doses and protracted courses of corticosteroids may not hinder CPI efficacy. However, differences in our primary endpoint PFS may be confounded by difference in BMI and rates of irAEs between each cohort, which are both known to be associated with improved CPI efficacy. Further analyses to account for these differences along with how timing of steroid initiation affects CPI-efficacy will be completed by time of presentation.

e15108 Background: Obesity is associated with 13 different cancer types, accounting for 40% of all cancers1. A few studies have linked a higher Body Mass Index (BMI) with longer Progression Free Survival (PFS) and Overall Survival (OS) from immune checkpoint inhibitors (CPI)s in patients with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma2,3,4. Our study evaluates CPI efficacy in patients with multiple tumor types in relation to Body Mass Index (BMI). Methods: We retrospectively collected data from patients treated with CPIs alone who also received steroids during their treatment from a single institution. This data included demographics such as age, sex, and BMI. Response and progression were defined per RECIST v1.1. The association of BMI and PFS was assessed by exact chi-square test. Kaplan Meier and Cox proportional hazard regression methods were used to estimate the survival probability and hazard ratios. Results: We identified a total of 129 overweight or obese patients (49%) with stage IV cancer who received CPI therapy. CDC guidelines define overweight as BMI > 25 and obese as BMI > 30. There was a significant relationship between PFS and BMI. Median PFS for those overweight was 287 days and 479 days for obese. Those with BMI 18.5-25 (normal), median PFS was 128 days and 103 days for those underweight (BMI < 18.5), (p = .0024). There was also a significant relationship between OS and BMI. Median OS for those obese was 751 days, for those overweight was 462 days. Median OS for those normal weight was 281 days and those underweight was 273 days (p = .0005). Obese patients had a 48% reduced risk of progression of disease/death as compared to those who had normal BMI (Hazard Ratio 0.52, p = .019). Overweight had a 31.5% relative risk reduction (HR 0.685, p = .05). Overall Response Rate was not significant between the two groups but there was a strong trend (p = .087). Conclusions: Higher BMI was associated with improved PFS and OS in patients with metastatic cancer across 20 different tumor types. Further investigation into the immune mechanisms behind this may lead to improvement in CPI efficacy for all patients.

e16050 Background: The PI3K/mTOR pathway overactivation and loss of PTEN occur in 20-40% of mCRC pts. A recent phase 1/2 study in mCRC pts showed evidence that everolimus added to 1L SOC treatment improved outcomes, in particular in pts with PTEN loss (Gilcrease, 2019). This prospective, single-arm phase 1/2 study aims to identify the optimal dose and schedule of nab-sirolimus (ABI-009), an mTOR inhibitor, plus FB and evaluate the safety and preliminary efficacy of this regimen. Methods: Eligible pts have no prior therapy, ≥18 years old, ECOG performance status of 0-2. PTEN loss (by IHC) is evaluated for all pts. nab-Sirolimus IV starting dose and schedule was 30mg/m2 weekly for 3 weeks followed by a week of rest (on D1, 8, and 15 in a 28-day cycle, qw3/4) plus standard doses of FB on D1 and D15. Dose escalation to 45 and 60mg/m2 or de-escalation to 20 and 10mg/m2 followed the 3+3 design. Dose limiting toxicity (DLT) was assessed in cycle 1. Results: As of Jan 31, 2020, 24 pts were treated in the phase 1 study and 18 were evaluable for response. No DLTs were observed in the first 3 pts treated with nab-sirolimus at 30mg/m2 qw3/4; however, all 3 pts missed D8 doses (due to G2 thrombocytopenia and G3 neutropenia) and the cohort expanded to additional 3 pts for further observation. 5/6 pts missed D8 doses and a new dose cohort enrolled pts at 20mg/m2 qw3/4. No DLTs were observed and the cohort was expanded to 10 pts. A safety review of the first 18 pts observed that 9/18 pts missed doses on D8 and a new cohort was added to enroll pts at 20 mg/m2 q2w (D1 and D15, as for FB). This cohort enrolled 8 pts with no DLTs and represents the recommended-phase-2-dose (RP2D) and continues enrollment in phase 2. For all pts, 15/24 (63%) pts had G3-4 treatment-related adverse events (TRAEs); most common were neutropenia (6/24, 25%) and thrombocytopenia (4/24, 17%). At the RP2D 3/8 (38%) pts had G3-4 TRAEs (thrombocytopenia, weight loss, and hypertension, 1 pt each). Among 18 evaluable pts, best response was: 7/18 (39%) partial response, 10/18 (56%) stable disease, and 16/18 (89%) had tumor shrinkage. PTEN was assessed in 14 pts: 4/14 (29%) had PTEN loss, 2/4 (50%) PTEN loss pts responded, while 3/10 (30%) pts that were PTEN+ (WT) had a response. Conclusions: The RP2D of nab-sirolimus is 20mg/m2 q2w in combination with standard mFOLFOX+bevacizumab. The phase 2 portion of the study is ongoing. Clinical trial information: NCT03439462 .

3059 Background: CBP501 is a 12-amino acid G2 checkpoint abrogator and calmodulin-modulating peptide that increases platinum influx into tumor cells and induces tumor immunogenic cell death. CBP501 also suppresses platinum-induced release of cytokines by macrophages, lowers cancer stem cell populations, and reduces migration, invasion, and epithelial-mesenchymal transition of tumor cells. We report safety and efficacy outcomes from dose-escalation and expansion cohorts of a Phase Ib study of CBP501 combined with cisplatin and nivolumab (NCT03113188). Methods: An open-label Phase I trial was conducted using a 3+3 design: CBP501 and cisplatin were dosed simultaneously by 1h infusion Q3W at 4 different combined dose levels (CBP501: 16 or 25 mg/m2; cisplatin: 60 or 75 mg/m2) in the dose-escalation cohort. Nivolumab (240 mg) was dosed on the same day as a 1h infusion following CBP501/cisplatin. CBP501 and cisplatin were fixed at 25 and 60 mg/m2, respectively, in the expansion cohort. Eligible patients had pathologically confirmed, locally advanced or metastatic solid tumors, age ≥18 years, ECOG PS 0-1, life expectancy > 3 months. The dose-expansion cohort had pretreated metastatic exocrine pancreatic cancer or microsatellite stable colorectal cancer (CRC). Scans were performed every 6 weeks while on study, then every 3 months. Results: The most common related adverse events (AEs) were infusion-related reaction (rash, itching, hives; n = 32/37 [Gr 1, n = 4; Gr 2, n = 28]; 86%) and anemia (n = 19/37 [Gr 1/2, n = 10; Gr 3, n = 9]; 51%). There were no additional safety signals other than those known for each agent. At January 9, 2020 (interim analysis), efficacy was evaluable in 17/19 patients in the dose-escalation cohort. Unconfirmed partial response was seen in 18% (3/17; 1 pancreatic, 1 colorectal, 1 cholangiocarcinoma), with > 3 months stable disease (SD) in 41% (7/17), disease control in 41% (7/17), and > 8 months overall survival (OS) in 53% (9/17). In the expansion cohort, efficacy was evaluable in 8/13 patients with pancreatic cancer: > 4 months SD was 50% (4/8), median progression-free survival 4.2 months, and median OS 5.9 months (6/8 ≥3rd line). The CRC cohort median OS for all CRC patients (n = 10) including the dose-escalation cohort (n = 5) was 17.5 months (10/10 ≥3rd line). Conclusions: The triple-drug combination is reasonably tolerable with preliminary signs of efficacy in refractory solid tumors, including those in which cisplatin and nivolumab have limited single-agent activity. Clinical trial information: NCT03113188 .

100 Background: Patients with a history of autoimmune disorders (AID) were generally excluded from immune checking inhibitor (CPI) trials because of concerns that these individuals might be at greater risk for developing serious immune-related adverse events (irAEs). This presents a knowledge gap, because a significant proportion of cancer patients also carry a diagnosis of AID. Methods: We retrospectively collected data from patients with AID treated with CPI at a single institution. irAEs were assessed using the CTCAEv5 criteria. Response was assessed using RECIST v1.1. Results: Of 47 cancer patients with a broad spectrum of malignancies and AIDs, 45% had active AID symptoms at the time of CPI initiation, of which 19% were on steroid-sparing agents (SSAs), 11% were on steroids, and 9% were on simultaneous steroids and SSAs. A total of 12 patients (25%) developed an AID flare, of which 100% were grade 1 or 2. Of these patients, 11 required systemic steroids, with 6 patients (55%) requiring greater than 12 weeks of oral steroids, and 3 patients required discontinuation of their CPI. Conventional irAEs developed in 10 patients (21%), of which 4 patients required systemic steroids, and 3 patients (27%) required discontinuation of their CPI. Efficacy outcomes for these patients, including radiographic response, will be available at time of data presentation. Conclusions: AID exacerbations or new irAES occurred in 25% and 21% of patients with a history of AID respectively, and were generally manageable. Only a minority of patients required cessation of their CPI due to toxicity.