Improving Survival in Advanced NSCLC: Multiple Lines of Chemotherapy Make a Difference
Oncologists who care for NSCLC patients need to develop management strategies.
Twenty years ago it there was a frequent debate as to whether or not advanced non-small cell lung cancer (NSCLC) was a treatable disease.1
In 1995, the NSCLC Collaborative Group published a meta-analysis2 evaluating the role of platinum-based chemotherapy in NSCLC. In advanced, metastatic NSCLC, cisplatin-based combination chemotherapy improved survival compared to best supportive care (BSC). The median survival time was improved by 2 months and 1-year survival rate was improved by 10% relative to BSC alone (the hazard ratio was 0.73, p<0.0001).
The demonstration that treatment in the second and third line also improved survival fostered the paradigm that multiple lines of therapy could significantly change the survival experience of these patients and was often associated with palliative relief of disease-related symptoms.3-5
The use of approved second- and third-line agents (docetaxel, pemetrexed, and erlotinib) as “maintenance” therapy also supported the concept that advanced, metastatic NSCLC was a treatable disease.
Mark A. Socinski, MD
Ho and colleagues6 have recently evaluated the use of first- and second-line chemotherapy in advanced NSCLC in a retrospective population-based review of the British Columbia Cancer Agency over a 10 year period. This time period spanned the approvals of docetaxel, pemetrexed, and erlotinib as second-line agents, which were based on randomized phase III trials.3-5
They demonstrated that the use of both first-line and second-line chemotherapy increased over the 10-year time period. Importantly, they also demonstrated that overall survival significantly increased with the increased use of multiple lines of therapy while no change was seen in the survival of patients receiving BSC.
This report reinforces the concept that advanced NSCLC, although incurable, is treatable. Meaningful gains in survival can occur but only if patients receive active therapies over time. One disturbing aspect of this report is that even in the most recent time period reported (2007), 67% of the patients did not receive chemotherapy and were managed by BSC.
This is even more shocking when one considers that 24% of the patients receiving BSC were said to have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1. The factors responsible for these high rates of non-treatment were not reported and are undoubtedly complex.
Failure to see a medical oncologist may often occur when the primary care physician is either not aware of the potential treatment effect or perceives that therapies may be too toxic. Certainly patient preferences are important and some patients may choose BSC versus active therapy. These high rates of non-treatment are not unique to this Canadian experience as others have reported that 40% to 50% of patients with advanced NSCLC do not receive chemotherapy.7,8
It is somewhat reassuring that the results of randomized clinical trials have influenced the care of this population of patients. It is surprising, however, that the uptake of new therapies and paradigms is relatively slow; the percentage of advanced NSCLC patients receiving second-line therapy increased from 21% in 1998 to 55% in 2007.
Although encouraging, medical oncologists caring for these patients need to develop management strategies to ensure that as close to 100% of patients receive second-line (and perhaps third-line) therapy given the survival and palliative benefits that have been demonstrated in randomized phase III trials leading to the approval of several agents for use in this setting by the U.S. Food and Drug Administration.
- Vokes EE, Bitran JD, and Vogelzang NJ. Chemotherapy for non-small cell lung cancer. The continuing challenge. Chest. 1991;99(6):1326-1328.
- Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ. 1995;311(7010):899-909.
- Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18(10):2095-2103.
- Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589-1597.
- Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123-132.
- Ho C, Ramsden K, Zhai Y, et al. Less toxic chemotherapy improves uptake of all lines of chemotherapy in advanced non-small-cell lung cancer: a 10-year retrospective population-based review. J Thorac Oncol. 2014;9(8):1180-1186.
- Ritzwoller DP, Carroll NM, Delate T, et al. Patterns and predictors of first-line chemotherapy use among adults with advanced non-small cell lung cancer in the cancer research network. Lung Cancer. 2012;78(3):245-252.
- Rasco DW, Yan J, Xie Y, et al. Looking beyond surveillance, epidemiology, and end results: patterns of chemotherapy administration for advanced non-small cell lung cancer in a contemporary, diverse population. J Thorac Oncol. 2010;5(10):1529-1535.