PURPOSE: The recruitment of underserved patients into therapeutic oncology trials is imperative. The National Institutes of Health mandates the inclusion of minorities in clinical research, although their participation remains under-represented. Institutions have used data mining to match patients to clinical trials. In a public health care system, such expensive tools are unavailable. METHODS: The NYU Clinical Trials Office implemented a quality improvement program at Bellevue Hospital Cancer Center to increase therapeutic trial enrollment. Patients are screened through the electronic medical record, tumor board conferences, and the cancer registry. Our analysis evaluated two variables: number of patients identified and those enrolled into clinical trials. RESULTS: Two years before the program, there were 31 patients enrolled. For a period of 24 months (July 2017 to July 2019), we identified 255 patients, of whom 143 (56.1%) were enrolled. Of those enrolled, 121 (84.6%) received treatment, and 22 (15%) were screen failures. Fifty-five (38.5%) were referred to NYU Perlmutter Cancer Center for therapy. Of the total enrollees, 64% were female, 56% were non-White, and overall median age was 55 years (range: 33-88 years). Our participants spoke 16 different languages, and 57% were non–English-speaking. We enrolled patients into eight different disease categories, with 38% recruited to breast cancer trials. Eighty-three percent of our patients reside in low-income areas, with 62% in both low-income and Health Professional Shortage Areas. CONCLUSION: Prescreening at Bellevue has led to a 4.6-fold increase in patient enrollment to clinical trials. Future research into using prescreening programs at public institutions may improve access to clinical trials for underserved populations.
The discovery of BRCA1 and BRCA2 in the 1990s revolutionized the way we research and treat breast, ovarian, and pancreatic cancers. In the case of pancreatic cancers, germline mutations occur in about 10–20% of patients, with mutations in BRCA1 and BRCA2 being the most common. BRCA genes are critical in DNA repair pathways, particularly in homologous recombination, which has a serious impact on genomic stability and can contribute to cancerous cell proliferation. However, BRCA1 also plays a fundamental role in cell cycle checkpoint control, ubiquitination, control of gene expression, and chromatin remodeling, while BRCA2 also plays a role in transcription and immune system response. Therefore, mutations in these genes lead to multiple defects in cells that may be utilized when treating cancer. BRCA mutations seem to confer a prognostic benefit with an improved overall survival due to differing underlying biology. These mutations also appear to be a predictive marker, with patients showing increased sensitivity to certain treatments, such as platinum chemotherapy and PARP inhibitors. Olaparib is currently indicated for maintenance therapy in metastatic PDAC after induction with platinum-based chemotherapy. Resistance has been found to these therapies, and with a 10.8% five-year OS, novel therapies are desperately needed.
1577 Background: Recruiting underserved patients onto therapeutic oncology trials is imperative in light of cancer disparities. Many institutions have increased enrollment with data mining tools that match patients to clinical trials, but such expensive tools are unavailable in a public safety net healthcare system. Methods: The NYU Perlmutter Cancer Center Clinical Trials Office implemented a quality improvement program aimed to increase therapeutic trial enrollment at Bellevue Cancer Center (BCC), an affiliated public hospital. The initiative utilized one employee to manually pre-screen patients via the EMR, cancer registries, and conferences. The program aimed to identify eligible patients for therapeutic trials and those subsequently enrolled. Results: During the two years preceding the pre-screening program, 31 patients were enrolled onto therapeutic clinical trials at BCC. For a period of two years (7/2017-7/2019) following the initiation of this program, 255 patients were identified, of which 143 (56.1%) enrolled onto trials. Of those enrolled, 55 were referred to NYU for trials not open at BCC. Among the 143 enrolled patients, 64% were female, 56% were non-white, and 57% did not speak English (spanning 16 languages). The median age was 55, and the top three disease groups were breast, GI, and thoracic. 83% of our patients reside in low-income areas, with 62% in both low income and Health Professional Shortage Areas (HPSA). Conclusions: Dedicating one employee to screening led to a 4.6 fold increase in accruals, successfully augmenting therapeutic trial enrollment in a healthcare setting with scarce resources, providing broader access to clinical trials for underserved populations.[Table: see text]
Molecular testing is performed upon diagnosis of non-small cell lung cancer (NSCLC) because of the large success of targeted therapies for oncogenic mutations. Epidermal growth factor receptor (EGFR) mutations are the most commonly identified mutation in NSCLC, and EGFR exon 20 insertion mutations (exon20ins) are the third most common mutation in EGFR following EGFR exon 19 deletions and exon 21 L858R mutations. EGFR exon20ins have regularly demonstrated resistance to classical EGFR inhibition. Two treatments-mobocertinib and amivantamab-have recently been the first drugs to be approved by the US Food and Drug Administration (FDA) for treatment of lung cancers with these mutations following platinum-based therapy. Research surrounding these two drugs demonstrates strong efficacy, but with an intense array of side effects. Another targetable driver mutation is the human epidermal growth factor receptor 2 (HER2) exon20ins, representing approximately 2-3% of NSCLC patients. This mutation has been heavily studied in vitro as well as clinically, and trastuzumab deruxtecan was just recently granted accelerated FDA approval based on the high efficacy demonstrated in the Destiny-Lung01 study. However, similar to their EGFR counterparts, HER2 inhibitors also have evidence of toxicity in clinical studies. In this paper, we discuss the limited response of EGFR and HER2 exon20ins to a wide range of standard treatment regimens, such as platinum-based chemotherapy and classic EGFR tyrosine kinase inhibitors, as well as immunotherapy. We also review recently approved and upcoming targeted therapeutic options, considering what research is presently being done regarding efficacy and the reduction of side effects, as well as the agents' risks and benefits for incorporation into an approved treatment regimen.
Background Checkpoint inhibitors (CPIs) targeting PD-1/PD-L1 and CTLA-4 have dramatically improved outcomes for a range of solid malignancies. irAEs from CPIs affect a wide range of tissues, vary in severity, and are difficult to predict. Multiple studies have reported on incidence of irAEs by immunotherapy type, but few have examined the association of irAEs with tumor histology or with sites of metastasis. This study aims to investigate the association between type and incidence of irAEs with type of solid tumor histology, as well as with sites of cancer metastasis. Methods We performed a retrospective analysis of all patients with genitourinary (GU), melanoma, gastrointestinal (GI), and lung malignancies treated with CPI monotherapy at the University of California, Irvine using an outpatient oncology pharmacy database. Data was collected from 1/1/2020 to 6/30/ 2021. Patients were aged 18 years and older. Patients must have received at least one dose of a CPI agent. Patients who received CPI-containing combination therapy with chemotherapy or targeted therapy were excluded. Results Of 423 patients on unique treatment lines in our data set, 268 patients received CPI monotherapy. irAEs were documented in 133 patients (49.6%). 71 patients (62.8%) required treatment with oral or intravenous steroids, and 42 patients (37.2%) received treatment with other supportive therapy. The incidence of irAEs based on tumor type is listed in table 1. Most common irAEs per tumor type were rash in GU malignancies (26.0%), colitis in melanoma (25.4%), rash in GI malignancies (29.3%), and pneumonitis in lung malignancies (60.0%). In patients with irAEs, 102 (76.7%) had metastatic disease and of those, 18 (17.6%) had an irAE involving a metastatic site (p<0.0001). In patients with irAEs involving the primary site of malignancy, 2 patients (4.7%) with renal cell carcinoma had nephritis, 12 patients (37.5%) with melanoma had dermatitis, and 2 patients (50%) with a lung malignancy had pneumonitis. Conclusions This study examines the differences in type and incidence of irAEs across GU, melanoma, GI, and lung cancers treated with CPI monotherapy. We found differences in the incidence of irAEs as relavant to tumor histology. Further, there was a statistically significant increased incidence of irAEs involving a metastatic site. Additional studies are needed, including those with a larger sample, combination immunotherapy and chemotherapy, as well as with additional tumor histologies. Ethics Approval Application #16536 for HS #2021-6843 titled, "Primary Cancer Histology and Sites of Metastatic Disease Correlate with Tissues Affected by Immune-Related Adverse Events" obtained approval by the University of California, Irvine Institutional Review Board. A waiver of consent was obtained as this study involved no more than minimal risk as it was a retrospective chart review.
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