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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 2
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
P1.14-04 - Final Results of the Prospective Genomics of Young Lung Cancer (GYLC), an Addario Lung Cancer Medical Institute Study (ID 427)
09:45 - 18:00 | Author(s): Alicia Sable-Hunt
We hypothesized that young age at lung cancer diagnosis is a clinical characteristic associated with a higher likelihood for having a driver mutation. Our goals were to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay groundwork for studies of heritable and environmental lung cancer risk factors.Method
Eligible subjects had a diagnosis of bronchogenic lung cancer < 40 years old. We included a website to allow for virtual consenting and remote participation from anywhere in the world. An integrated data and biorepository allowed for completion of study activities and routing of specimens. We defined seven genes of interest based on the Lung Cancer Mutational Consortium (LCMC): EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET. We hypothesized that the prevalence of targetable alterations in these genes would be greater in our population compared to the LCMC and powered our study to detect an increase from 35% to 50%. Subjects with advanced adenocarcinoma who were not tested for all seven genes or who were wild type for all seven underwent additional genomic profiling using Foundation Medicine testing.Result
We accrued 133 participants from July 2014 to June 2017. Notably, 44% entered the trial via the website. The mean age at diagnosis was 34 (range 16 to 39) and 57% were female; 77% were stage 4 at diagnosis and the majority had adenocarcinoma (86%). Of the 115 patients with adenocarcinoma, 83.5% were stage 4 and the focus of the comparison to the LCMC cohort. A targetable mutation was identified in 85.4%, with 76% harboring a combined ALK (38.5%), EGFR (31.3%), or ROS1 (6.3%) mutation. Of 14 patients who underwent on-protocol testing, a targetable driver was identified in eight (57%), including two with a RET rearrangement, two with ERBB2 mutations, two with MET amplification, one with an ALK rearrangement with a prior negative FISH and one with a novel EGFR-RAD fusion previously tested negative for EGFR.Conclusion
We have described a genomically distinct subset of NSCLC in patients < age 40. Those with stage 4 adenocarcinoma must undergo comprehensive genomic testing to identify a targetable driver. The extremely high rate of driver mutations particularly in ALK supports the need for an Epidemiology of YLC study. Additionally, use of remote consenting and the Addario Lung Cancer Foundation's advocacy enabled rapid accrual of this rare cohort (<1%) and has laid the foundation for innovative research partnerships with other rare oncogene-driven patient groups.
P1.14-29 - Disrupting the Paradigm: Partnering with Oncogene-Focused Patient Groups to Propel Research (ID 1498)
09:45 - 18:00 | Author(s): Alicia Sable-Hunt
Genomic alterations drive more than 60% of adenocarcinoma cases of non-small cell lung cancer (NSCLC). About 20% of cases will have an oncogenic driver (EGFR, ALK, ROS1, BRAF, NTRK, etc.) that can be treated with approved targeted therapy drugs, and more (RET, Exon 20 insertions, etc.) have clinical trial options. Patients and caregivers dealing with these cancers have organized globally into oncogene-focused groups (“Groups”—see Table 1) and are building partnerships that seek to provide support, increase awareness and education, accelerate and fund research, and improve access to effective diagnosis and treatment.
We partnered in a variety of ways to accelerate research. While each Group sets its own research priorities, we’ve found successful collaborative research has the following seven characteristics. It includes patients from the start, in all aspects of the project. It addresses questions meaningful to patients. It develops patient-centered measurements. It accommodates patients’ clinical realities. It leverages social media and patient groups. It shares progress with participants frequently. It makes results rapidly and freely available.Result
These methods have enabled the Groups to collaborate successfully with clinicians, researchers, advocacy organizations, and industry to generate ideas for next steps in research for their disease, forge new studies and clinical trials for a specific oncogenic driver, create new patient-derived models of oncogene-driven cancers to study acquired resistance, develop registry-based studies to collect real-world data, and guide patients to clinical trials.Conclusion
Oncogene-focused patient-caregiver groups are creating new paradigms across the research continuum. They have demonstrated that their partnerships with advocacy organizations, clinicians, researchers, and industry, can increase available patient-derived models, patient data, and specimens among geographically distributed, oncogene-driven cancer populations.
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