Lung cancer is the most common cause of cancer death in the United States, and 85 to 90 percent of lung cancers are non-small cell (NSCLC). Although cancer treatments are approved on the basis of prospective clinical trials, retrospective analyses of existing clinical and translational databases have a potential for highly clinically relevant hypothesis generation or validation.
To that end, the Thoracic Oncology TCE maintains several ongoing clinical and translational databases. These databases have been critical in supporting clinical/translational projects, obtaining industry funding and in providing preliminary data for NIH grants.
Surgically Treated NSCLC Patients
Surgical resection remains the primary treatment for patients with stage I and II NSCLC. The role of surgery for stage III disease is controversial, while stage IIIB or IV patients are rarely surgical candidates. Better characterization of the clinical “profile” of responders to surgery is needed.
The Thoracic TCE maintains a database of lung cancer patients who have undergone resection at the hospital of The University of Pennsylvania. Data include demographics, smoking history, date of diagnosis, pathology and radiology information, mutation status (where available), date of surgery, type of surgery, history of previous/post-up chemo, recurrence data, outcome and survival data. In a subset of these patients, these data are also linked to translational data including myeloid cell phenotypes, cytokine production of tumor digests, IHC and mRNA levels (nanostring).
EGFR-TKI Treated NSCLC Patients
The emergence of molecular testing and the introduction of targeted therapies have led to dramatic improvement in the overall survival of patients with advanced NSCLC. The EGFR and TP53 genes are commonly mutated in NSCLC patients with independent prognostic implications, but the significance of the coexistence of these mutations as well as other “incidental” mutations in patients with advanced NSCLC is not well established.
To determine the prognostic impact of TP53 mutations and other coexisting mutations in EGFR-mutant NSCLC patients, the TCE has developed and maintained a database of demographic, clinical, molecular and follow-up information on EGFR-mutant advanced or recurrent NSCLC patients seen at the Abramson Cancer Center of the University of Pennsylvania starting 2008. Using this database, we have retrospectively reviewed the clinical course of EGFR-mutant NSCLC patients and compared the clinical outcome according to their TP53 status and coexisting mutation status. (Significant findings are being prepared for publication.)
To better delineate the association of EGFR mutations with different outcomes in NSCLC patients treated with tyrosine kinase inhibitors (TKIs), the TCE maintains and updates a database of EGFR-mutated NSCLC patients receiving TKI treatment at the University of Pennsylvania’s Abramson Cancer Center.
Anti PD-1/PD-L1 Treated NSCLC Patients
In 2015, the PD-1 inhibitors nivolumab and pembrolizumab were approved by the FDA for the second-line treatment of both squamous and non-squamous advanced/metastatic NSCLC; atezolizumab, a PD-L1 inhibitor was similarly approved in 2017. In addition, single agent pembrolizumab is now FDA approved in the front line setting in patients with PD-L1 expression levels of 50 percent or higher. Novel markers of outcomes are needed to define the select patient population who will derive durable benefit from PD-1 and PD-L1 antibodies.
To better characterize the clinical “profile” of responders to PD-1 and PD-L1 antibodies, the TCE maintains a database of all patients treated with these agents at the University of Pennsylvania. Using this database, we conducted a retrospective cohort study of all patients with previously treated advanced NSCLC who initiated nivolumab at the Abramson Cancer Center of the University of Pennsylvania between the date of nivolumab initial approval by the US FDA, and March 1, 2016. (Novel findings were published in the Journal of Lung Cancer, Bagley, et. al.; see publications.)
Studies with other PD-1 and PD-L1 inhibitors, pembrolizumab and atezolizumab are ongoing. Furthermore, we now have one of the largest clinical experiences with these agents in current clinical practice. Thus, we have more mature data to compare outcomes.
Custom Databases: Meeting Your Specific Needs
Led by Christiana Davis, MD, (in collaboration with Peter Gabriel, MD, MSE, Chief Oncology Informatics Officer and Abigail Doucette, MPH, Research Registry Program Manager), the Thoracic TCE has established project-based databases to track response of patients to immune-oncology treatments, as well as acquired resistance to standard therapies and novel targeted immunotherapies.
Using recently enhanced search tools that allow us to screen the Penn Data Store, EPIC, Text Information Extraction System (TIES) and other electronic medical records to identify patients with specific characteristics, the Thoracic TCE creates tailored databases (REDCap and/or Spreadsheets) to meet specific projects’ needs.
These project-based databases have also become a crucial link in the identification and development of novel markers of outcome.
Collaboration with Our TCE
The TCE supports collaboration. To learn more, please contact us.
Corey Langer, MD: Corey.Langer@uphs.upenn.edu
Steven Albelda, MD: Albelda@mail.med.upenn.edu
Christiana Davis, MD: Christiana.Davis@uphs.upenn.edu