Dr. Garth Nicholas, University of Ottawa oncologist, has co-authored a case report with our own Andrea Redway, Stage 4 RET+ non-small cell lung cancer (NSCLC) patient who successfully responded to immune checkpoint inhibitor (ICI) therapy for seven years. "Proud to have published a case report with the patient herself as a co-author," tweeted Dr. Nicholas. "I hope this becomes a more standard practice as our patients continue to teach 'nothing about us without us.'"
ICIs - specifically those targeting PD-1/PD-L1 - are routinely used in advanced NSCLC patients, but a majority do not respond. ICIs also pose a risk of immune-related adverse events (IrAE) and are costly. Dr. Nicholas and other researchers are thus exploring biomarkers that may better predict likelihood of ICI response.
Andrea was diagnosed with Stage IV NSCLC in 2015. She discontinued chemotherapy after three cycles due to significant gastrointestinal toxicities and mixed response on CT scans. She subsequently received genetic testing that revealed a RET-KIF5B fusion, along with a PD-L1, PD-L2 and JAK2amplification. She then started ICI.
Andrea responded robustly to ICI for seven years, when her cancer began to progress. She started the first-generation RET-targeted therapy Retevmo in 2022, which was not available even in trial settings until nearly two years after her diagnosis. Her cancer is now stable. "My response to nivolumab (ICI) has been extraordinary, particularly given that we had limited information to guide decision-making as well as limited treatment options in 2015," writes Andrea. "Yet 7 years later, I am well and have more treatments options available than when I was diagnosed."
Dr. Nicholas hypothesizes that Andrea's PD-L1/PD-L2/JAK2 amplification accounted for her particularly robust, long-term ICI response. "Although amplification of this gene cluster is rare in NSCLC adenocarcinoma, it is a meaningful and actionable finding," he writes. "This raises the question whether routine genetic testing for PD-L1/PD-L2/JAK2 amplification could optimize the choice of upfront systemic therapy and ultimately improve outcomes in this patient cohort."
The RET community is grateful to Dr. Nicholas for his critical research into potentially better genomic predictors of ICI response. Andrea's case study suggests that more routine genetic testing for PD-L1/PD-L2/JAK2 amplification could identify a patient cohort with greater potential for ICI response.
As a patient community, we are also grateful for the inclusion of the patient voice in this case report. We are especially grateful to and proud of Andrea for her work as a patient advocate. "Knowledge that I have PD-L1 amplification and the RET fusion alteration have been a source of needed optimism and hope for me and my family as we have lived through this challenging journey," writes Andrea. "I hope that my case study will contribute to research that will generate more viable treatment options for lung and other cancer patients. I also hope that it will provide needed optimism and hope for patients and their families as we move closer to finding a cure."
Read the full case report.