To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis.
Adult patients with solid tumors were treated in ...four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort.
Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube cancers had partial remissions for 5.2 and 9.2 months.
5F9 is well tolerated using a priming dose at 1 mg/kg on day 1 followed by maintenance doses of up to 45 mg/kg weekly.
Background
Enfortumab vedotin (EV) is a novel antibody‐drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate ...Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials.
Methods
UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were ed from chart reviews by investigators at each site. The observed response rate (ORR) was investigator‐assessed for patients with at least 1 post‐baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy.
Results
The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression‐free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06).
Conclusions
In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate < 30 mL/min and significant comorbidities.
Lay Summary
Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer.
This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations.
Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real‐world setting, and support the use of this drug in broader patient populations.
On the basis of initial data from the Urothelial Cancer Network to Investigate Therapeutic Experiences study, enfortumab vedotin has activity in diverse populations of patients with urothelial cancer, including patients with variant histologies, patients with FGFR3 alterations, and patients with significant comorbidities previously excluded from clinical trials. Additionally, in this large, multi‐institutional, retrospective cohort of patients with urothelial cancer, responses to enfortumab vedotin in patients treated outside a clinical trial are consistent with and complementary to prior clinical trial data.
Renal cell carcinoma (RCC) subtypes differ in molecular characteristics and prognosis. We investigated the associations of RCC subtype with patient demographics, comorbidity, and neighborhood ...socioeconomic status (nSES).
Using linked California Cancer Registry and Office of Statewide Health Planning and Development data, we identified history of hypertension, diabetes, and kidney disease prior to RCC diagnosis in Asian/Pacific Islander, non-Latino Black, Latino, and non-Latino White adults diagnosed with their first pathologically confirmed RCC from 2005 through 2015. We used multinomial multivariable logistic regression to model the association of demographics, comorbidity, and nSES with clear-cell, papillary, and chromophobe RCC subtype.
Of the 40,016 RCC cases included, 62.6% were clear cell, 10.9% papillary, and 5.9% chromophobe. The distribution of subtypes differed strikingly by race and ethnicity, ranging from 40.4% clear cell and 30.4% papillary in non-Latino Black adults to 70.7% clear cell and 4.5% papillary in Latino adults. In multivariable analysis, non-Latino Black individuals had a higher likelihood of presenting with papillary (OR, 3.99; 95% confidence interval, 3.61-4.42) and chromophobe (OR, 1.81; 1.54-2.13) versus clear-cell subtype compared with non-Latino White individuals. Both hypertension (OR, 1.19; 1.10-1.29) and kidney disease (OR, 2.38; 2.04-2.77 end-stage disease; OR, 1.52; 1.33-1.72 non-end-stage disease) were associated with papillary subtype. Diabetes was inversely associated with both papillary (OR, 0.63; 0.58-0.69) and chromophobe (OR, 0.61; 0.54-0.70) subtypes.
RCC subtype is independently associated with patient demographics, and comorbidity.
Targeted RCC treatments or RCC prevention efforts may have differential impact across population subgroups.
•Low socioeconomic status and Black patients with stage II nonseminomatous germ cell tumors (NSGCT) are less likely to receive retroperitoneal lymph node dissection.•Medicaid and/or uninsured ...patients with stage III NSGCT are less likely to receive retroperitoneal lymph node dissection.•Low socioeconomic status NSGCT patients of all stages have increased cancer-specific mortality.•Black patients with stage I and II disease had increased cancer-specific mortality.
Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs).
Within the Surveillance Epidemiology and End Results database (2005–2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality.
Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40–0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15–1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46–0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27–0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12–6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48–16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively.
This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.
Background
Patient reported outcomes (PROs) have been associated with improved symptom management and quality of life in patients with cancer. However, the implementation of PROs in an academic ...clinical practice has not been thoroughly described. Here we report on the execution, feasibility and healthcare utilization outcomes of an electronic PRO (ePRO) application for cancer patients at an academic medical center.
Methods
We conducted a randomized trial comparing an experimental ePRO arm to standard of care in patients with advanced cancer in the thoracic, gastrointestinal, and genitourinary oncology groups at Stanford Cancer Center from March 2018 to November 2019. We describe the pre-implementation, implementation, and post-implementation phases of the ePRO arm, technological barriers, electronic health record (EHR) integration, clinician burden, and patient data privacy and security. Feasibility was pre-specified to be at least 70% completion of all questionnaires. Acceptability was based on patient and clinician feedback. Ambulatory healthcare utilization was assessed by reviewing numbers of phone messages, electronic portal messages, and referrals for supportive care.
Results
Of 617 ePRO questionnaires sent to 72 patients, 445 (72%) were completed. Most clinicians (87.5%) and patients (93%) felt neutral or positive about the ePRO tool’s ease of use. Exposure to ePRO did not cause a measurable change in ambulatory healthcare utilization, with a median of less than two phone messages and supportive care referrals, and 5–6 portal messages.
Conclusions
Web-based ePRO tools for patients with advanced cancer are feasible and acceptable without increasing clinical burden. Key lessons include the importance of pilot testing, engagement of stakeholders at all levels, and the need for customization by disease group. Future directions for this work include completion of EHR integration, expansion to other centers, and development of integrated workflows for routine clinical practice.
The NCCN Clinical Practice Guidelines in Oncology recommend definitive therapy for all men with high-risk localized prostate cancer (PCa) who have a life expectancy >5 years or who are symptomatic. ...However, the application of these guidelines may vary among ethnic groups. We compared receipt of guideline-concordant treatment between Latino and non-Latino white men in California.
California Cancer Registry data were used to identify 2,421 Latino and 8,636 non-Latino white men diagnosed with high-risk localized PCa from 2010 through 2014. The association of clinical and sociodemographic factors with definitive treatment was examined using logistic regression, overall and by ethnicity.
Latinos were less likely than non-Latino whites to receive definitive treatment before (odds ratio OR, 0.79; 95% CI, 0.71-0.88) and after adjusting for age and tumor characteristics (OR, 0.84; 95% CI, 0.75-0.95). Additional adjustment for sociodemographic factors eliminated the disparity. However, the association with treatment differed by ethnicity for several factors. Latino men with no health insurance were considerably less likely to receive definitive treatment relative to insured Latino men (OR, 0.34; 95% CI, 0.23-0.49), an association that was more pronounced than among non-Latino whites (OR, 0.63; 95% CI, 0.47-0.83). Intermediate-versus high-grade disease was associated with lower odds of definitive treatment in Latinos (OR, 0.75; 95% CI, 0.59-0.97) but not non-Latino whites. Younger age and care at NCI-designated Cancer Centers were significantly associated with receipt of definitive treatment in non-Latino whites but not in Latinos.
California Latino men diagnosed with localized high-risk PCa are at increased risk for undertreatment. The observed treatment disparity is largely explained by sociodemographic factors, suggesting it may be ameliorated through targeted outreach, such as that aimed at younger and underinsured Latino men.
Cancer patients frequently develop tumor and treatment-related complications, leading to diminished quality of life, shortened survival, and overutilization of emergency department and hospital ...services. Outpatient oncology treatment has potential to leave cancer patients unmonitored for long periods while at risk of clinical deterioration which has been exaggerated during the COVID19 pandemic. Visits to cancer clinics and hospitals risk exposing immunocompromised patients to infectious complications. Remote patient reported outcomes monitoring systems have been developed for use in cancer treatment, showing benefits in economic and survival outcomes. While advanced devices such as pulmonary artery pressure monitors and implantable loop recorders have proven benefits in cardiovascular care, similar options do not exist for oncology. Here we review the current literature around remote patient monitoring in cancer care and propose the use of reliable devices for capturing and reporting patient symptoms and physiology.
The response to the COVID-19 pandemic has affected the management of patients with cancer. In this pooled retrospective analysis, we describe changes in management patterns for patients with cancer ...diagnosed with COVID-19 in two academic institutions in the San Francisco Bay Area.
Adult and pediatric patients diagnosed with COVID-19 with a current or historical diagnosis of malignancy were identified from the electronic medical record at the University of California, San Francisco, and Stanford University. The proportion of patients undergoing active cancer management whose care was affected was quantified and analyzed for significant differences with regard to management type, treatment intent, and the time of COVID-19 diagnosis. The duration and characteristics of such changes were compared across subgroups.
A total of 131 patients were included, of whom 55 were undergoing active cancer management. Of these, 35 of 55 (64%) had significant changes in management that consisted primarily of delays. An additional three patients not undergoing active cancer management experienced a delay in management after being diagnosed with COVID-19. The decision to change management was correlated with the time of COVID-19 diagnosis, with more delays identified in patients treated with palliative intent earlier in the course of the pandemic (March/April 2020) compared with later (May/June 2020) (OR, 4.2; 95% CI, 1.03 to 17.3;
= .0497). This difference was not seen among patients treated with curative intent during the same timeframe.
We found significant changes in the management of cancer patients with COVID-19 treated with curative and palliative intent that evolved over time. Future studies are needed to determine the impact of changes in management and treatment on cancer outcomes for patients with cancer and COVID-19.
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