bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and unique pharmacokinetic profile of ARX788, a site-specific ADC, in heavily pretreated patients with HER2-overexpresing solid tumors: Results from two phase 1 clinical trials.
Authors: Hurvitz Sara A. , Park Haeseong , Frentzas Sophia , Shannon Catherine M. , Cuff Katharine , Eek Richard Wilhelm , Budd George Thomas , McCartney Amelia , O'Shaughnessy Joyce , Lu Janice M. , Zhang Jian , Ji Dongmei , Shen Weina , Li Matt , Yan Jinchun , Xia Gang , Ji Yanping , Yao Sulan , Xiong Gaozhun , Hu Xichun
Published: June 2021

1038

Background: ARX788 is a site-specific, homogeneous, and highly stable ADC. The payload AS269 is conjugated to the synthetic amino acids para-acetylphenylalanine (pAF) in a humanized anti-HER2 mAb. ARX788 demonstrated promising activity in HER2-positive, HER2-low, and T-DM1 resistant tumors in preclinical studies. Here we present the phase 1 clinical data evaluating the safety, antitumor activity, and PK of ARX788 in advanced solid tumors. Methods: The standard 3+3 design (0.33 - 1.5 mg/kg; Q3W or Q4W) is used to determine the MTD and/or RP2D in two phase 1 studies in HER2-positive solid tumors in U.S. and Australia (ACE-Pan tumor-01) and in HER2-positive breast cancers in China (ACE-Breast-01). The efficacy endpoints include ORR and DCR. Intensive PK sampling in first 3 cycles is performed to characterize serum PK profiles of ARX788, total Ab, and pAF-AS269. Results: 69 and 34 heavily pretreated patients received ARX788 monotherapy in the ACE-Breast-01 (median 6 prior lines of therapy) and ACE-Pan tumor-01 trial (including breast, gastric/GEJ, NSCLC, ovarian, urothelial, biliary track, endometrial, and salivary gland cancer) respectively. Dose escalation for both studies have been completed with no DLT reported. MTD has not been reached. ARX788 was generally well tolerated with most AEs being grade 1 or 2. The most common grade >3 AEs include ocular AEs (5.7 %) and pneumonitis (4.3%) in the ACE-Breast-01 trial; pneumonitis (2.9%) and fatigue (2.9%) in the ACE-Pan tumor-01 trial. Low systemic toxicities in terms of the incidence rate and grade (as shown in table). No treatment-related death. In the 1.5 mg/kg cohort, ORR was 74% (14/19) and 67% (2/3) for ACE-Breast-01 and ACE-Pan tumor-01, respectively. DCR was 100%. Median DOR or median PFS has not been reached. PK profiles for total antibody and ARX788 were generally comparable across all dose levels. Mean T1/2 for ARX788 and total antibody had approximately 100 hours at the dose of 1.5 mg/kg. Serum pAF-AS269 concentrations peaked with a median time of 168 h. Serum exposure of pAF-AS269 was low with the Cmax and AUC at cycle 1 being approximately 0.1% and 0.18% of those for ARX788 on a molar basis, respectively. Conclusions: High stability of ARX788 and low serum exposure of pAF-AS269 may underlie the low systemic toxicity, which differentiates it from other ADCs. Clinical trial information: NCT032550070 .[Table: see text]
Clinical impact of medical policy supporting universal germline testing for patients with colorectal cancer.
Authors: Nielsen Sarah M. , Dalton Joline , Hatchell Kathryn E. , DaCosta Byfield Stacey , Moretz Chad , Buresh John , Hall Taryn , Nussbaum Robert Luke , Esplin Edward D.
Published: June 2021

10514

Background: Colorectal cancer (CRC) affects approximately 104,000 patients (pts) annually in the United States, up to 45% of which are estimated to be genetic and/or familial. Aligned with clinical guidelines, in 2020, a large U.S. insurer established Medical Policy allowing for and reimbursing germline genetic testing (GGT) for all CRC pts. This study reports overall uptake of GGT in CRC pts under this inclusive policy, actionable findings and treatment implications for pts tested, stratified by self-reported ancestry/ethnicity. Methods: Two independent de-identified datasets were reviewed, including administrative claims data of commercially insured and Medicare Advantage enrollees, aged 18+ with CRC (≥1 claim with ICD10 C18, C19 or C20 in the first position) who were continuously enrolled (CE) in the health plan from 1/2019-10/2020. Evidence of genetic testing based on CPT codes, was examined during 2020. A second de-identified dataset of CRC pts whose GGT was billed to the insurer under the Medical Policy, was also reviewed. Patient demographics, clinical information and GGT results were descriptively analyzed. Results: Of the >18,000,000 CE enrollees, 55,595 were identified as CRC pts, of whom 1,675 (3%) received GGT. From the GGT dataset, 788 pts had test results available for review. 143 (18%) pts had pathogenic/likely pathogenic (P/LP) variants in genes including MSH2, MLH1, PMS2, MSH6, CHEK2, APC, BRCA2, ATM, MUTYH (biallelic). Of pts with P/LP variants, 96 (67%) were potentially eligible for precision therapy and/or clinical treatment trials. Overall, 133 (93%) had P/LP variants in genes with precision therapy, clinical trial and/or published management implications. In a subset of pts (n=674) with ethnicity data; Asian, Black/African-American and Hispanic pts showed lower relative uptake of germline testing than Caucasians (Table). Conclusions: Despite Medical Policy allowing for GGT for all pts with CRC, only 3% of eligible pts received testing. If all CRC pts had been tested, these data suggest up to 6,705 pts with P/LP variants conferring potential eligibility for precision therapy (PD-1/PD-L1 inhibitors) or clinical treatment trials (PARP inhibitors), and an additional 2,602 pts with mutations in genes with published management recommendations, could have been identified, but were missed. Additional research is needed to identify obstacles to systematic implementation of this Medical Policy, the best timing of GGT to prevent CRC and improve access to underrepresented populations. CRC patients with germline genetic testing.[Table: see text]
Cancer-specific mortality associated with germline genetic testing results among women with breast cancer or ovarian cancer treated with chemotherapy.
Authors: Kurian Allison W. , Abrahamse Paul , Hamilton Ann S. , Deapen Dennis , Gomez Scarlett Lin , Morrow Monica , Berek Jonathan S. , Katz Steven J. , Ward Kevin C.
Published: June 2021

10517

Background: Breast and ovarian cancer patients increasingly undergo germline genetic testing. While studies suggest a greater chemotherapy benefit for carriers of BRCA1/2 pathogenic variants, little is known about whether pathogenic variants in other genes are associated with cancer mortality. Methods: Georgia and California Surveillance, Epidemiology and End Results (SEER) registry records of women diagnosed with breast cancer or ovarian cancer from 2013-2017 were linked to results of clinical germline genetic testing from four participating laboratories. Patients were included if they linked to a genetic result, had stages I-III breast cancer or I-IV epithelial ovarian cancer and received chemotherapy. Multivariable Cox proportional hazard models were used to examine the association of genetic results, demographic and clinical factors with cancer-specific mortality. Results: 21,348 breast and 4,320 ovarian cancer patients were analyzed with median follow-up of 41 months. Pathogenic variants were present in 12% of patients with estrogen and progesterone receptor-positive, HER2-negative breast cancer, 9% with HER2-positive breast cancer, 17% with triple-negative breast cancer and 18% with ovarian cancer. Pathogenic variants were most common in BRCA1/2, CHEK2, PALB2, ATM and BRIP1. Among triple-negative breast cancer patients, mortality was lower with pathogenic variants in BRCA1 (hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.17-0.45) and genes other than BRCA1/2 (HR 0.33, CI 0.13-0.81) versus no pathogenic variant. Genetic results were not associated with mortality in other breast cancer subtypes. Among ovarian cancer patients, mortality was lower with pathogenic variants in BRCA2 (HR 0.36, CI 0.26-0.49) and in genes other than BRCA1/2 (HR 0.48, CI 0.33-0.70). Conclusions: Among breast and ovarian cancer patients treated with chemotherapy, those with germline pathogenic variants in several cancer-associated genes had equivalent or lower short-term mortality than those testing negative. These results may guide patient counseling and clinical trial design.
Chemoprotective effect of metformin against HR+/HER2- breast cancer among women with type-2 diabetes.
Authors: Chikermane Soumya , Abughosh Susan M. , Sharma Manvi , Trivedi Meghna V. , Aparasu Rajender R. , Johnson Michael L.
Published: June 2021

10518

Background: Type-2 diabetes mellitus (T2DM) increases the risk of breast cancer among postmenopausal women. Metformin has demonstrated a chemoprotective effect in breast cancer, however its role in HR+/HER2- breast cancer (HR+/HER2- BC), the most common subtype, has not been studied among older women with T2DM in the United States. This study evaluated if increased exposure to metformin is associated with a reduced risk of HR+/HER2- BC among postmenopausal women with T2DM. Methods: A case-control study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2008-2015). Those diagnosed with HR+/HER2- BC as their first/only cancer after incident T2DM diagnosis were cases. The event date was the date of HR+/HER2- BC diagnosis in cases, and randomly assigned to non-cancer T2DM controls based on the distribution in cases. Cases were matched to up to 4 controls each using incidence density sampling with replacement. Metformin exposures were defined as cumulative dose, average intensity and adherence, measured during the 1-year lookback period prior to the event date. Dose (mg) was categorized as: 0, 0-30,000, 30,001-136,000, 136,001-293,000, and > 293,000. Average intensity per day (mg/day) was categorized as: 0, 1-500, and > 500. To evaluate adherence, those without metformin claims during the lookback period were excluded. Adherence measures were: binary proportion of days covered (PDC) (≥0.80, < 0.80) and adherence trajectories. Group based trajectory modeling was used to identify trajectories (adherent, slow decline, rapid decline, and early discontinuation). The Anderson Behavioral Model was used to guide selection of covariables: demographic and clinical variables (diabetes severity, metabolic syndrome, comedications, and health status). Conditional logistic regression was used to evaluate the association between exposure to metformin and the risk of HR+/HER2- BC. Results: The main cohort included 690 cases and 2747 controls. A decremental reduction in odds of HR+/HER2- BC in the highest cumulative dose (OR = 0.72, 95% CI: 0.55-0.95; OR = 0.60, 95% CI: 0.42-0.85) and intensity (OR = 0.61, 95% CI:0.46-0.82) categories of metformin was observed compared to the no-metformin group. Those non-adherent to metformin had 45% (OR = 1.45, 95% CI: 1.08-1.94) increased odds of HR+/HER2- BC compared to those adherent. The risk of HR+/HER2- BC in the adherent (OR = 0.67, 95% CI: 0.39-1.14), slow decline (OR = 0.75, 95% CI: 0.43-1.32) and rapid decline (OR = 0.73, 95% CI: 0.41-1.31) trajectories was not statistically significant compared to the early discontinuation trajectory. Conclusions: This retrospective study based on SEER-Medicare found an association between high dose and intensity of metformin use with reduced odds of incidence of HR+/HER2- BC among postmenopausal women with T2DM. Adherence to metformin also showed protective effect against HR+/HER2- BC.
Reductions in cancer screening: The consequence of changes in routine care during the COVID-19 pandemic.
Authors: Kim Ashley , Gitlin Matthew , Fadli Ela , McGarvey November , Cong Ze , Chung Karen
Published: June 2021

10550

Background: The COVID-19 pandemic imposes significant impact on daily activities with regard to public health orders and individual responses to the pandemic. Much of the direct or indirect impact is potentially in reductions in healthcare encounters for services such as preventive care. Here, we quantified changes in cancer screening rates to better understand the impact of the evolving COVID-19 implications and shifts in health-seeking behaviors. Methods: We conducted a retrospective analysis of cancer screening rates during March-June 2019 (pre-COVID-19) and March-June 2020 (post-COVID-19 restrictions), using Optum’s de-identified Clinformatics Data Mart Database which includes Medicare and commercially insured members. Members meeting age and/or sex criteria as detailed in the United States Preventive Services Task Force recommendations for breast, colorectal, lung, prostate, and cervical cancer screening represented the eligible membership for screening. Procedure and laboratory services were used to identify those who received cancer screening. Analyses were conducted cross-sectionally by cancer screening type. Results: Eligible cohorts were identified from insured members within March-June 2019 and 2020 (2019: 17,931,318; 2020: 17,521,411). The percent of eligible members screened in March-June 2019 was 19.3%, 9.4%, 16.7%, 0.4%, and 7.8% for breast, cervical, prostate, lung, and colorectal cancer, respectively. Changes in screening rates from 2019 to 2020 are summarized in Table, with the sharpest decline in April. The percent change from 2019 to 2020 during the combined March-June period for each cancer screening type was statistically significant (p<0.0001). Conclusions: Routine cancer screening rates from March-June 2020 showed meaningful reductions when compared to the same period in 2019, with substantial declines during the initial peak of the pandemic in April. These declines may be impacted by variations in regional restrictions with tighter restrictions leading to larger screening declines and loosening restrictions reflecting catch-up screening. Efforts to promote cancer screening in a safe and timely manner are crucial given individual risk factors, to reduce later stage cancer diagnoses and improve clinical outcomes.[Table: see text]
Young-onset colorectal cancer: A call for action.
Authors: Baraibar Iosune , Salva Francesc , Comas Raquel , Ros Javier , Garcia Ariadna , Sanchis Mireia , Cuadra Jose Luis , Saoudi Nadia , Valdivia Augusto , Mulet Nuria , Virgili Ana , Hernando Jorge , Capdevila Jaume , Martí Marc , Landolfi Stefania , Verdaguer Helena , Espin Eloy , Nuciforo Paolo , Tabernero Josep , Elez Elena
Published: June 2021

10563

Background: Young-onset colorectal cancer (YOCR) is defined as diagnosis below the age of 50. Over the past decades, the incidence of YOCRC has increased at an alarming rate, but causes and pathogenesis still remain unknown. Early detection of colorectal cancer (CRC) has demonstrated to improve survival. Despite these facts, adults < 50 years old are not yet included in screening programs and YOCRC is not well characterized. We aimed to characterize the clinical and molecular characteristics of YOCRC in patients (pts) diagnosed at our institution. Methods: Consecutive pts with a diagnosis of CRC below the age of 50 visited for the first time at Vall d’Hebron University Hospital in Spain between January 2017 and October 2020 were included in the analysis. Data of clinicopathologic features and treatment were collected retrospectively from medical records. Results: 205 pts met the inclusion criteria, 111 (54%) were females, 8 (4%) presented a personal history of cancer at diagnosis and 109 (53%) a family history of cancer. Age at diagnosis was: < 30: 10 (5%), {30 – 40): 52 (25%), {40-45): 51 (25%), {45-50): 92 (45%). Site of primary tumor was: right colon: 50 (24%), left colon: 107 (52%): rectum: 48 (24%). Stage at diagnosis was I: 3 (1%), II: 14 (7%), III: 60 (29%), IV: 128 (63%). 6 of 14 (43%) and 44 of 60 patients (73%) with stage II and III CRC presented disease progression after initial treatment, respectively. Molecular status was: KRAS mutation: 74 (36%), NRAS mutation: 7 (3%), BRAF mutation: 12 (6%), MSI-H: 12 (6%). 43 pts (21%) had documentation of genetic counseling. Median (range) number of lines of treatment for metastatic disease was 3 (1-7), 53 pts (30%) received at least 4 lines of treatment. Median (range) number of metastatic sites was: 2 (1-6). 114 patients (55.6%) had died at the cut-off timepoint. Conclusions: YOCR is usually diagnosed with a more advanced stage than standard-onset CRC, with a poorer course of the disease. Further studies in young adults with CRC should address this phenomenon to understand the underlying causes, and prioritize genetic counseling. Our results support the unmet need of initiating screening programs in adults younger than 50 years, the urgency for a global consensus and a call for action.
Point of care genetic testing in a breast cancer survivorship clinic.
Authors: Ranallo Lori , Nye Lauren Elizabeth , Williams Mary , Fabian F.A.S.C.O Carol J. , O'Dea Anne , Klemp Jennifer R.
Published: June 2021

10580

Background:: Breast cancer survivorship care (BCSC) includes the ongoing assessment of personal and family cancer history and offering genetic education, counseling and testing to survivors who meet NCCN, ASBrS and Medicare guidelines for germline genetic testing. It is reported that approximately 8% of patients with breast cancer (BC) will have a clinically actionable germline mutation. However, lower than expected rates of testing are seen in both the acute and extended phases of BCSC. We sought to identify the number of patients seen in a long-term survivorship clinic who had previously undergone or currently qualified for germline testing, and the prevalence of germline variants in BC survivors. Methods: In a Nurse Practitioner (NP) led clinic, 2,184 non-selected BC survivors were screened to determine if: germline testing was previously completed or if update germline testing or initial germline testing is needed (with a 3-generation review of family history). BC survivors eligible for initial or update germline testing (411 patients) were provided with genetic education, counseling, and offered multigene panel testing. Seven (7) BC survivors declined testing. Results: From May 2019 – January 2021, 2,184 BC survivors were seen in the clinic. The average age of survivors = 60.2 yrs; average time since diagnosis = 10.7 yrs; and average age at diagnosis = 50.1 yrs, gPV were identified in 10.4%. Out of pocket cost on average was $50.00 for 2.0% of those tested. Conclusions: Within a comprehensive Breast Cancer program where genetic testing is common practice, there is an ongoing need to screen breast cancer (BC) survivors for genetic testing eligibility. A significant number of BC survivors will test positive for a pathogenic mutation (10.4%) a decade after an initial diagnosis. Genetic testing is a necessary step to stratify a BC survivors’ risk of developing secondary cancers, appropriate screening and prevention strategies, cascade testing, and for some, treatment planning. This individualized approach to BCSC is often described, but difficult to put into action. Time/access and drop rates with a referral model are barriers. Incorporating a point of care genetic testing model requires additional support (genetic extender), professional development, education, and a commitment to provide patient centric care.[Table: see text]
Germline testing and somatic tumor testing for BRCA1/2 pathogenic variants in ovarian cancer: What is the optimal sequence of testing?
Authors: Kwon Janice S. , Tinker Anna , Santos Jennifer , Compton Katie , Sun Sophie , Schrader Kasmintan A. , Karsan Aly
Published: June 2021

10585

Background: In 2020 ASCO recommended that all women with epithelial ovarian cancer have germline testing (GT) for BRCA1/2 mutations, and those without a germline pathogenic variant (PV) should have somatic tumor testing (TT), to determine eligibility for PARP inhibitor (PARPi) therapy (GT-TT strategy). An alternate strategy is to start with tumor testing first, and to conduct germline testing only in those with a PV in the tumor, or a significant family history (TT-GT strategy). The objective was to conduct a cost-effectiveness analysis comparing the 2 testing strategies. Methods: A Markov Monte Carlo simulation model compared the costs (USD) and benefits of the 2 testing strategies. According to local empiric data, a sufficient tissue sample for TT was available in 99% of cases, otherwise the patient would only have GT. Sensitivity of TT was 99% for detecting germline PV. Only those with BRCA1/2 PV were eligible for PARPi. Primary outcomes included the number of women eligible for PARPi, with progression-free years of life (PFLY) gained based on SOLO1 data, and the incremental cost-effectiveness ratio (ICER). Monte Carlo simulation estimated the number of women who would have GT and TT, and the total with germline or somatic BRCA1/2 PV eligible for PARPi. Sensitivity analyses accounted for uncertainty around various parameters. Results: The GT-TT strategy was more effective but more costly than TT-GT in identifying patients eligible for PARPi. Table summarizes the average lifetime costs, benefits, and Monte Carlo simulation estimates for 10,000 women diagnosed with advanced epithelial ovarian cancer annually in the USA. The incremental benefit from the GT-TT strategy would be achieved at substantial cost to the health care system, with an ICER of $119,340 per PFLY gained relative to the TT-GT strategy. The results were highly sensitive to the sensitivity of TT to detect germline PV, and the costs of GT and TT. Assuming that GT was less than 50% of the cost of TT, the sensitivity of TT had to exceed 98% for the TT-GT strategy to be cost-effective. Conclusions: Although the ASCO recommended strategy of BRCA germline testing followed by tumor testing for those without a pathogenic variant may be more effective in identifying ovarian cancer patients for PARP inhibitor therapy, it is more costly. The ASCO strategy is justified if the sensitivity of tumor testing is not sufficiently high. However, assuming high tumor testing performance rates, tumor testing first followed by germline testing if there is a PV in the tumor and/or family history is a cost-effective strategy.[Table: see text]
Multicancer hereditary syndrome testing: Genetic counselors’ perspectives.
Authors: Weldon Christine B. , Liang Su-Ying , Phillips Kathryn A , Douglas Michael P , Scheuner Maren Theresa , Kurian Allison W. , Schaa Kendra , Roscow Breanna , Erwin Deanna , Trosman Julia Rachel
Published: June 2021

10594

Background: The accessibility of cancer hereditary syndrome testing has increased, and the cost has declined significantly in the past few years. We conducted a national, quantitative survey of genetic counselors (GCs) to assess their perspectives on what influences hereditary cancer genetic testing decisions and practices, with a focus on cost. This survey was funded by NIH, conducted by UCSF TRANSPERS, and supported by the National Society of Genetic Counselors (NSGC). Methods: The survey was developed through literature review, expert interviews, and a pilot. Sent to the NSGC Cancer Special Interest Group via email. Chi-square tests were used to examine variability. Results: The survey response rate was 56% (202/363). Multiple hereditary cancer syndrome tests are discussed often/always by 86% of genetic counselors (GCs). The existence of an institutional protocol on multiple hereditary cancer syndrome testing was reported by 35.4% of GCs. When asked about GC counseling encounters, GCs report insurance rarely/never pays for: 25.2% pre-test in-person, 39.7% for pre-test tele-genetics, 35.4% post-test in-person, and 52.9% post-test tele-genetics. GCs rated clinical factors higher than cost as influencing decision for multiple hereditary syndrome cancer testing (table); the total cost of the test was least important. These patterns were similar across the GCs institution types and years in practice. Conclusions: We found consistent use of multiple hereditary cancer syndrome tests, with less focus on cost, out-of-pocket, and insurance coverage and more of a focus on clinical indicators. GCs reported challenges with reimbursement for GC counseling encounters. The shift toward more genetic counseling encounters via tele-genetics necessitates evaluation of insurance reimbursement.[Table: see text]
Relative risk of pneumonitis or interstitial lung disease (ILD) associated with the use of cyclin-dependent kinase inhibitors (CDK4/6i): A systematic review and meta-analysis of phase 3 randomized controlled trials.
Authors: Jahan Nusrat , Wongsaengsak Sariya , Rehman Shabnam , Vinan-Vega Myrian , Tijani Lukman Aderoju , Hardwicke Fred L.
Published: June 2021

1072

Background: All three currently approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) such as palbociclib, abemaciclib, and ribociclib are reported to cause significant pulmonary toxicities including fatal pneumonitis or interstitial lung disease (ILD). We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of pneumonitis or ILD associated with CDK4/6i. Methods: We conducted a systematic search using PRISMA guidelines in PubMed, EMBASE, American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meeting abstracts from inception through Jan 30, 2021. Phase 3 RCTs using CDK4/6i in the intervention arm and reporting the number of events for pneumonitis or ILD were included in the analysis. The Cochran-Mantel-Haenszel method and random effects model were used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested by Cochran’s Q test and I2 value. Results: Five phase 3 RCTs — MONALEESA-3, MONALEESA-7, MONARCH plus, monarchE, and PALLAS — reported the number of events for any grade pneumonitis or ILD and were included in the final analysis. A total of 13,191 patients — 6,758 in the CDK4/6i arm and 6,433 in the control arm — were analyzed. Following regimens were used in CDK4/6i arms — MONALEESA-3: ribociclib + fulvestrant; MONALEESA-7: ribociclib + tamoxifen or a non-steroidal aromatase inhibitor + goserelin; MONARCH plus: in cohort A, abemaciclib + anastrozole or letrozole, and in cohort B, abemaciclib + fulvestrant; MonarchE: abemaciclib + standard-of-care adjuvant endocrine therapy (ET); PALLAS: Palbociclib + ET. In the control arms, all studies used placebo and respective endocrine therapies. Any grade pneumonitis or ILD was reported in 1.64% of patients in the CDK4/6i arm versus 0.68% of patients in the control arm. The pooled RR of any grade pneumonitis or ILD was 2.26, 95% CI: 1.60-3.19, P < 0.00001, I2 = 0%. Grade 3/4 pneumonitis or ILD was reported in 0.28% of patients in the CDK4/6i arm and 0.06% of patients in the control arm with pooled RR of 2.35, 95% CI: 0.37-15.08, P = 0.37, I2 = 34%. One grade 5 pneumonitis was reported in the monarchE. Conclusions: Cyclin-dependent kinase 4/6 inhibitors are associated with increased risk of any grade pneumonitis or ILD. Early detection and prompt initiation of appropriate interventions are vital to reduce the morbidity and mortality associated with CDK4/6i induced pneumonitis or ILD.
Novel approach to improve the diagnosis of pediatric cancer in Kenya via telehealth education.
Authors: Severance Tyler , Olbara Gilbert Kipruto , Njuguna Festus , Treff Marjorie , Loehrer Patrick J. , Vik Terry A.
Published: June 2021

11000

Background: Childhood cancer has an annual incidence of 150-160 cases per million children worldwide but remains vastly under-diagnosed in low to middle income countries (LMIC) such as in Sub-Saharan Africa. Moi Teaching and Referral Hospital (MTRH) is the only tertiary referral hospital in western Kenya and serves a population of 25 million people, including 10 million children. The average number of pediatric cancer diagnoses was 216 cases annually in 2017-2019, well below the anticipated 1500 cases based on cancer epidemiology data. We recently completed a comprehensive Needs Assessment suggesting that due to inadequate pediatric oncology education, many clinical diagnoses are missed and correct diagnostic tests are not obtained at county hospitals. Local medical staff expressed interest in educational programs to help augment their understanding and diagnostic evaluation of pediatric oncology. Methods: To address these disparities in medical knowledge, we implemented Project ECHO – a validated virtual guided practice and telementoring model – to connect multidisciplinary specialists at MTRH with staff in medically underserved communities in western Kenya for ongoing training, technical assistance, and mentorship. The ECHO program follows a Hub-and-Spoke design where the specialists at MTRH and pediatric oncologists at Riley Hospital functioned as the “hub” team and the health care workers at county hospitals were the “spokes”. Sessions were freely available on Zoom twice monthly and featured both a didactic topic presented by experts and a spoke-led case-based discussion. The discussion utilized dialogue education to promote learning and engagement among the spokes with mentorship from the hub team. Results: The ECHO program launched successfully in January 2020 with a curriculum focused on pediatric oncology for general health care workers. A total of 22 sessions occurred with an average of 23 learners (primarily staff at community hospitals within the referral region) per session. Despite the COVID-19 pandemic, the year-end analysis in January 2021 demonstrated 286 new pediatric patients were diagnosed with cancer at MTRH representing a 33% increase over the 3-year average. Conclusions: The implementation of a telehealth education platform – Project ECHO – focused on diagnosing pediatric cancer in medically underserved communities in Kenya, is a useful model to increase the recognition and earlier referral of childhood cancer in LMICs.
Analysis of hematology and oncology fellowship website content and diversity representation.
Authors: Muthiah Arun , Aggarwal Vanya , Wei Chapman , Muthiah Chandrasekar , Quesenberry Matthew I. , Dizon Don S.
Published: June 2021

11004

Background: Fellowship in hematology and oncology (HO) is widely sought after but lags behind all other internal medicine subspecialties in attracting applicants underrepresented in medicine (URM). An approach to appealing to URMs involves preexisting in-person strategies but also adapting virtual tools to promote inclusion. Specifically, program websites serve as the first impressions of a program, as well as influence the perception of diversity and inclusion. We evaluated the content and diversity representation of HO program websites to facilitate a generally more informed and URM-considerate recruitment. Methods: The websites of 2019-2020 ACGME accredited HO programs were assessed between June 1st to July 1st, 2020. Data focused on 30 informational categories, derived from published methodology, along with three additional categories concerning diversity, based on suggestions for inclusive graduate medical education recruitment strategies, were compared using two-tailed t tests. We defined websites with 70% or more of the 30 informational categories as “comprehensive websites.” Affiliation with a National Cancer Institute (NCI) Designated Cancer Center, NCI Designated Cancer Center + National Cancer Center Network (NCCN) member institution, and a top 50 ranked cancer hospital by U.S. News was also considered in the analysis. Results: A total of 156 program websites were analyzed: 37.2% NCI; 19.9% NCCN; 29.5% U.S. News ranked. Only 31 (19.9%) were “comprehensive websites,” and 34 (21.8%) had information pertaining to at least one of the diversity categories. There was a significant association between inclusion of diversity content and being a “comprehensive website” (p = 0.001). Compared to those that were neither designated nor ranked, programs designated by NCI, NCCN, or ranked by U.S. News were more likely to have more complete information available (p < 0.001, = 0.008, and < 0.001, respectively). However, only programs ranked by U.S. News were more likely to include information about diversity on their websites (p = 0.006). Conclusions: The vast majority of HO fellowship program websites were not comprehensive, including a lack of diversity and inclusivity content. NCI designation, NCCN participation, and US News ranking were significantly associated with more complete fellowship websites. Given the context of the COVID-19 pandemic in which institution visitation is restricted, program websites may have elevated importance in recruitment. HO programs should direct resources to offering more complete and inclusive websites to better inform applicants, including URM residents.
NCI Awardee Skills Development Consortium (NASDC): Applicant profiles.
Authors: Verschraegen Claire F. , Hashibe Mia , O'Connell Ann , Neill Ushma , Rodriguez Romina , Pirl William F. , Gray Tamryn , Yusufov Miryam , Hexner Elizabeth , Mankoff David A. , Noel Cauleen , Romney Madeline , Korczak Jeannette , Matthews Lindsay , Jedidi Iness , Jackson Rebecca
Published: June 2021

11030

Background: In 2020, the NCI funded a new educational consortium, NASDC (NCI Awardee Skills Development Consortium, RFA-CA-19-010 and -011), through four institutionally granted UE5 awards to deliver a specific course each and a U24 award as a Coordinating Center. The goal is to teach current early-career faculty NCI grantees skills in areas critical for successful independent academic cancer research careers. Courses focus on leadership and socioemotional skills, health disparities, immuno-oncology, and cell and gene therapy. Teaching will initially be virtual, given the COVID pandemic. Methods: A steering committee and four working groups were established to build the consortium infrastructure, including the NASDC (osu.edu) website. Clientele are early-career faculty PD/PI of a current NCI-funded grant (K01, K07, K08, K22, K23, K25, R00, R21, DP1, DP2, DP5, R01, R23, R29, R37, R56, RF1, RL1, U01), of whom 454 were directly contacted. Blast emails and social media were also used. We are reporting the characteristics of 154 applicants, who completed the RedCap application online. Results: 85% of the applicants are within the first 5 years of a faculty appointment, 87% at the assistant professor rank, and 65% on tenure track. 40% hold an M.D. degree and 72% a Ph.D. 81% are US citizens, 52% females, and 45/33/16/2/4%-11% are White/Asian/Black/Native Americans/Other–Hispanics/Latino. 76% work at NCI-designated comprehensive cancer centers. Mean protected research time is 80%. Non-mutually exclusive fields of research interest are therapeutics (46%), basic science (37%), disparities (34%) prevention (32%), public health (28%), and pediatrics (10%). 66% have received a K-award grant, 13% each an R21 or R00, and 3% an R01. Additionally, 35% had a second NCI grant as PI, 10% a third grant, and 60% had non-NCI grants. Reasons for applying included (1) not quite ready to lead a research team (42%), (2) need for stronger career mentoring (37%), and (3) not being fully confident in research skills (21%). Conclusions: Applicants to the new NCI educational consortium (NASDC) have a successful start to their academic career with a third having obtained more than one NCI award. Most applicants work at NCI-designated comprehensive cancer centers. As cancer research continues to evolve and has the potential to address critical health care needs of the nation, NASDC will strive to equip scientists to be leaders, teach advances in technology, and impart confidence in research skills.
Impact of #ASCO Twitter impressions on the oncology community.
Authors: Morgan Gilberto , Choueiri Toni K. , Patel Ronak , Balaji Kavitha , Subbiah Vivek
Published: June 2021

11039

Background: The oncology community is embracing social media (SM) platforms like Twitter to gain exposure to research, to network, and to engage in real-time discussions. The emergence of SM activity around the ASCO annual meetings has dramatically increased over the past 5 years, with factors such as the COVID-19 pandemic further accelerating use of digital platforms. This growth in SM engagement within the oncology community has previously been presented by totaling the quantity of tweets within a given time frame. Here, we explore the impact of specific trends through impression data. Methods: To evaluate activity trends among certain oncology stakeholders, we utilized an SM analytics platform, Symplur, to conduct a content analysis around ASCO conferences (2016-2020) using hashtags (#ASCOyy) as the search criterion. We focused our analysis on trends in impressions , defined by the theoretical maximum number of Twitter users a given tweet could have directly reached in a follower's timeline. We gathered impressions data to quantitatively assess overall ASCO engagement and evaluate topics of interest, and to discover common ASCO themes and reach within specific stakeholder groups. Results: Our results show the largest increase in impressions was during #ASCO20, despite a plateauing effect seen in the actual number of tweets (Table). The cumulative number of impressions for #ASCO16 was 468.2 million compared with approximately 1.12 billion for #ASCO20. Differentiating this result from the number of tweets related to ASCO, there was stabilization in the absolute number from #ASCO17 onward. When compiling impressions by doctors and by patient advocates, a similar trend emerged, with the most impressions captured during #ASCO20 (Table). Conclusions: As SM use continues to expand in the oncology community, stakeholders have turned to their digital voice to express views and opinions. The impact of impressions versus absolute number of tweets will continue to grow with a stakeholder’s follower count, thus building on the digital presence in oncology.[Table: see text]
A phase 2 study using ipilimumab, nivolumab, and trabectedin for previously untreated metastatic soft tissue sarcoma.
Authors: Gordon Erlinda Maria , Chua Victoria S. , Kim Ted T. , Chawla Neal Shiv , Brigham Don Arlen , Bhuiyan Ishrat , Agulnik Mark , Chow Warren Allen , Chawla Sant P. ,   Sarcoma Oncology Center Staff
Published: June 2021

11562

Background: Sarcoma cells are most immunogenic earlier in the disease course and before treatment when the immune system can recognize and destroy them. Hypothesis: Immune checkpoint inhibitors would be most effective when given to previously untreated patients with metastatic soft tissue sarcoma. Methods: Eligible patients for this Phase 2 study are previously untreated patients ≥ 18 years of age with unresectable or metastatic soft tissue sarcoma, with measurable disease by RECIST v1.1. Immune checkpoint inhibitors Ipilimumab (I) and Nivolumab (N) were given with Trabectedin (T), a marine derived alkaloid with defined doses of I (1 mg/kg i.v. q 12 weeks), N (3 mg/kg i.v. q 2 weeks), and T (1.2 mg/m2 i.v. q 3 weeks). Primary endpoints: (1) Objective response rate by RECIST v1.1 via CT scan or MRI, (2) Progression-free survival (PFS): from first day of treatment to disease progression or death due to any cause; otherwise, it is censored at the time of last follow-up, and (3) Overall survival: from first day of treatment to death due to any cause; otherwise, it is censored at the time of last follow-up. Results: There were eighty-two evaluable subjects, having completed the first cycle of I, N, and T and have had a CT or MRI scan at the 6-week follow-up period. Best Overall Response by RECIST v1.1 = 7 CR (2 surgical CR), 9 PR, 54 SD, and 12 PD. Disease control rate was 85.4%. The median PFS was >6.4 (range: 0-32) months; 6-month PFS rate: 57.3%. The median OS was >12.0 (0-38) months; 6-month OS rate: 78.8%. Safety analysis: The most common Grade 3 TRAEs include increased ALT (26), anemia (11), increased AST (9), and fatigue (8). Common Grade 4 TRAEs include thrombocytopenia (2), increased AST (2), increased ALT (2), and increased CPK (2). There was one Grade 5 TRAE of rhabdomyolysis (1). Conclusions: Taken together, these results suggest that first-line combinatorial therapy with I, N, and T are (1) synergistic, and (2) may be equal or superior to, and safer than, standard first line therapy for advanced/metastatic soft tissue sarcoma. Clinical trial information: NCT03138161.
Comprehensive geriatric assessment and management for Canadian elders with Cancer: The 5C study.
Authors: Puts Martine , Alqurini Naser , Strohschein Fay , Monette Johanne , Wan-Chow-Wah Doreen , Koneru Rama , Szumacher Ewa , Mehta Rajin , Mariano Caroline Joy , Li Anson , Hsu Tina , Brennenstuhl Sarah , Mclean Bianca , Wills Aria , Amir Eitan , Krzyzanowska Monika K. , Elser Christine , Pitters Eric , Breunis Henriette , Alibhai Shabbir M.H. ,   5C Study Team
Published: June 2021

12011

Background: Comprehensive Geriatric Assessment (CGA) is recommended by ASCO for older adults with cancer undergoing chemotherapy to identify issues that can interfere with treatment delivery and optimize functional status and quality of life. However, few randomized controlled trials have been completed so far. Our objective is to evaluate the effectiveness of CGA on improving quality of life for older adults receiving cancer treatment. Methods: Eligible patients were aged 70+, diagnosed with a solid tumour, lymphoma or myeloma, referred for first/second line chemotherapy, speaking English/French, and with an Eastern Collaborative Oncology Group Performance Status 0–2. The CGA was done by a nurse and geriatrician followed by monthly phone calls by the study nurse for 6 months. Patients were randomly assigned (1:1) to receive either the intervention (CGA plus follow-up by geriatric trained team in addition to usual oncology care) or usual care alone. All participants received a monthly healthy aging booklet for attention control. Randomization was stratified by center and treatment intent (curative/adjuvant versus palliative). Our primary outcome was health-related quality of life (HRQOL) assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health scale (items 29 and 30). Secondary outcomes include functional status (Instrumental Activities of Daily Living). Outcome data collection was completed monthly for the first 6 months, then at 9 and 12 months. For the primary outcome we used a pattern mixture model using an intent-to-treat approach (at 0, 3, and 6 months). The last data collection took place March 8 2021. Results: From May 2017 to March 2020, 351 participants from 8 hospitals across Canada were enrolled. All patients were seen on or after day 1 of treatment for the intervention per patient request. Patient characteristics at baseline were similar in both arms. The average age was 75.7 (SD = 4.8), 60.4% was male and 54.3% had treatment with palliative intent. Change in HRQOL scores did not differ by arm (p =.80). Neither group exceeded the MCID of 10 points. There was also no difference in IADL between the groups (p = 0.82). Conclusion: CGA was not effective in improving quality of life for older adults receiving cancer treatment in this study. CGA may need to be performed prior to treatment initiation to achieve benefits. Clinical trial information: NCT03154671.
Immunotherapy toxicity in patients over 65 years.
Authors: Mendez Miriam , Cantos Blanca , Nuñez García Beatriz , Sanchez Juan Cristobal , Franco Fernando , Maximiano Constanza , Gutiérrez Lourdes , De La Puente Blanca , Ruíz Casado Ana , Provencio Mariano
Published: June 2021

12027

Background: Cancer patients increasingly present an advanced age at diagnosis; 50% of the new cases are over 65 years old, being underrepresented in clinical trials. The safety of immunotherapy has not been adequately evaluated in the subgroup of elderly patient. In this population, with more comorbidities, adverse events may be less well tolerated and have more serious consequences. Methods: A retrospective observational study was developed, including all patients treated with immunotherapy at our center between January 2015 to February 2020. Of the total (279 patients), the analysis was performed with the 105 patients ≥65 years of age who had received at least one cycle (in routine clinical practice or within an unblinded clinical trial). All clinical and radiological data of the patients were collected. Results: From the total, the majority had a lung carcinoma or melanoma, treated with nivolumab or pembrolizumab either in first or second line. 63% had died at the time of the analysis. The frequency of toxicities: digestive (15%), pneumonitis (12%) and endocrine (9%). We divided the population into 65-75 years (76 patients) or > 75 years (29 patients), analyzing the frequency of toxicity and deaths secondary to it. Those > 75 years had more digestive toxicity (25% vs 11%), but less pneumonitis (3% vs 15%). There were 7 deaths (6%) related to treatment: 2 patients with ipilimumab-nivolumab (28%), 2 nivolumab (28%), 2 pembrolizumab (28%), and 1 ipilimumab (16%). 5 patients were > 75 years old (median 78 years) presenting a higher mortality rate in relation to toxicity (4% vs 20%, p 0.02) and a worse median survival (29 vs 23 months). The fatal toxicities were: 3 neurological (2 meningoencephalitis and 1 acute diffuse axonal denervation), 2 hepatic, 1 hemophagocytic syndrome and 1 myocarditis. Conclusions: The most frequent toxicity was digestive, but those that led to death were neurological, hepatic, hematological and cardiac. In our series, neurological and cardiac adverse events accounted for 57% of immunotherapy deaths in older patients. Our data warn that patients over 75 years have a higher risk of death from immune-mediated events. In addition, these would be mainly neurological and cardiac, which represents a diagnostic and treatment challenge for oncologists.[Table: see text]
Can patients with advanced malignancy and poor performance status benefit from nivolumab plus ipilimumab as a palliative treatment?
Authors: Abughanimeh Omar Khaled , Sharma Smriti , High Robin , Krishnan Mridula , Teply Benjamin A.
Published: June 2021

12028

Background: Performance status (e.g. Eastern Cooperative Oncology Group [ECOG] score) is a predictive tool used to determine whether a patient may benefit from cytotoxic chemotherapy. The toxicity profile of immunotherapy is different, and less is known about whether performance status (PS) is similarly associated with toxicity and benefit. Nonetheless, most clinical trials for immune checkpoint inhibitors have excluded patients with poor PS. Emerging data by our group and others has linked poor PS with lack of response and decreased survival with anti-PD-1/L1 agents, but whether combination therapy abrogates the poor outcomes of PD1 only therapy is unknown. Methods: We conducted a retrospective cohort study of patients with metastatic cancer who received ipilimumab plus nivolumab at our institution between January 2014-December 2020. We compared outcomes between those with good PS (Group A, ECOG PS 0-1) and poor PS (Group B, ECOG PS ≥ 2). Our primary outcomes were overall survival (OS) and incidence of grade 3-4 immune-related adverse events (irAEs). Other outcomes included objective response rates and need for hospitalization. We utilized the Kaplan-Meyer method for time to survival analysis and exact Pearson Chi-squared testing for response, toxicity, and hospitalization analysis. Results: A total of 129 patients were identified with a mean age of 59.9 years. Among them were 73 males (57%) and 56 females (43%). Malignant melanoma was the most common malignancy (39%) followed by renal cell carcinoma (27%), small cell lung cancers (10%), non-small cell lung cancers (9%), and the rest with other histologies. 113 patients (87.6%) were in group A and 16 (12.4%) in group B. Across all tumor types, patients in Group B had significantly worse OS compared to group A (HR 0.24 [0.13-0.48], P = < 0.0001). Group B similarly had higher rates of hospitalization compared to group A (94% vs 56%, P = 0.0048). Interestingly, irAEs were not driving these hospitalizations, with a trend toward lower rates of irAEs in the poor PS group (19% vs 46% in Group A, P = 0.057). The overall response rate in group B was numerically lower (6% vs 26% in group A, p = 0.1). Conclusions: Our study showed that using ipilimumab plus nivolumab in patients with poor PS was associated with significantly poorer OS and higher rates of hospitalizations. irAEs were not increased in the poor PS group, suggesting a lack of treatment efficacy seemed to driving these poor outcomes. Extrapolation of clinical trial data for ipilimumab-nivolumab to a broader population including those with poor PS should be done with caution. Unfortunately, our data showed that most patients with poor PS were not adequately palliated with ipilimumab-nivolumab.