Some 190,000 Americans will be diagnosed with non-small cell lung cancer (NSCLC) this year, with more than half being diagnosed with metastatic disease. Unfortunately, these stage IV patients have historically faced often dismal prospects for survival, and most are unlikely to survive the first year after diagnosis. While new treatment options have led to small but meaningful improvements over the years, there are still a substantial number of patients who are not treated with newer systemic therapies. In a recent issue of The Oncologist, Drs. Joshua Roth, Bernardo Goulart, and Scott Ramsey in the Public Health Sciences Division quantified the survival gains provided by these new therapies over time, and simulated the potential further improvements in survival that could be made with further uptake of systemic therapies.
In 1990, the expected one- and three-year survival for metastatic NSCLC cases was only 14% and 3%, respectively, with a mean expected survival time of only 8.6 months. At the time, best supportive care (BSC) was the only op oo d tion. Since then, the advent of various first-line systemic therapies has raised hope for longer survival. These include single agent platinum therapies, multiple generations of platinum-doublet therapies, monoclonal antibody strategies, and biomarker-directed targeted therapies. “Given that survival for patients with stage IV NSCLC is relatively poor,” said lead author Dr. Roth, “it can be difficult for patients and providers to know whether we have made progress in helping patients live longer with this disease.” To quantify this improvement, the authors developed a simulation model that estimated overall survival for metastatic NSCLC patients from 1990 to 2015.
Image from Dr. Josh Roth
The authors incorporated data from the several sources to model overall survival across this 25-year time period. The Surveillance, Epidemiology, and End Results (SEER) database provided the proportions of patients receiving any systemic therapies, while a commercial database provided the market share of particular regimens by year. Primary literature and clinical trial results provided systemic therapy uptake and expected survival duration for given therapies. Modeling these data together, the authors estimated the increase in expected survival for each 5-year period. Over 25 years, expected one- and three-year survival doubled to 28% and 6%, respectively, translating to a gain in life expectancy of 4.2 months (to 12.8 months total). Given the high incidence of NSCLC, these increases also amount to a meaningful number of additional life years on a population level.
Roughly half of these survival gains could be attributed to systemic platinum-doublet therapies. Surprisingly, however, only about 40% of patients were receiving these treatments in 2015. Said Roth, “we don’t know why more than 60% of advanced NSCLC patients don’t get any systemic therapy. One important issue may have been lack of insurance, since many of these patients are low income.” By modeling scenarios with higher proportions of patients receiving systemic therapy, the authors demonstrated that additional survival gains are possible. They found that a 10% increase could raise the expected one-year survival to 32%, with a life expectancy of 13.7 months, while a 30% increase could raise these to 38% and 15.5 months. Given the high incidence of NSCLC, these small but meaningful per-patient improvements could still mean large population-level life-year gains.
“The future is brightening for these patients,” said Roth. “Increased availability of genomic testing and the development of targeted therapies with more favorable toxicity profiles versus traditional cytotoxic regimens are improving options for these patients. The question is whether future patients will avail themselves of these therapies. Increases in the treated proportion are not a foregone conclusion, and efforts are needed to educate patients and clinicians about the changing landscape of advanced NSCLC treatment and the benefits and risks of new treatment options. It remains to be seen whether these gains can be realized in the coming years in the face of potential repeal the Affordable Care Act, a trend toward cancer patients paying an increasing share of their treatment costs, and other potential barriers. We will be monitoring these issues and continuing this conversation in the literature and in the broader cancer outcomes research community.”
Funding for this study was provided by Genentech and the Agency for Health Research and Quality.
Roth JA, Goulart BH, Ravelo A, Kolkey H, Ramsey SD. 2017. Survival Gains from First-Line Systemic Therapy in Metastatic Non-Small Cell Lung Cancer in the U.S., 1990-2015: Progress and Opportunities. Oncologist. 22(3):304-310. doi: 10.1634/theoncologist.2016-0253.