Pfs versus Os Endpoint in Nsclc

non-small-cell lung cancer (nsclc), median survival in untreated patients is only 4–5 months, with a survival rate at 1 year of 10%2. Since the year 2000, significant advances have been made in the treatment options for advanced nsclc, including cytotoxic agents and targeted therapies; and in a select group of patients, current treatments offer median survival rates that approach 2 years3. Overall survival (os), defined as the time from randomization to death from any cause, is a direct measure of clinical benefit to a patient. Patients alive or lost to follow-up are censored4. Overall survival offers the greatest clinical gain, provided that quality of life (qol) is not compromised. As an endpoint, os is easily measured, unambiguous, objective, felt to be clinically significant, and unaffected by the timing of assessment. However, measuring os as an endpoint in clinical trials requires large patient numbers and increased length of follow-up, thus potentially delaying the approval of new agents. With the therapeutic options for patients with advanced nsclc increasing, there are concerns that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That concern is based on the assumption that subsequent lines of therapy are more effective in the control arm than in the treatment arm, or that the biology of the treatment arm has changed in some way because of exposure to the study drug, making further treatments less effective—both of which are not supported by evidence5. Also, time to death unfortunately remains relatively short in advanced nsclc compared with time to death in breast and colorectal cancer, thus weakening the argument that os requires prolonged follow-up for lung cancer patients. Nonetheless, with the increased success of systemic treatments, there is a need to have efficacious drugs available to patients earlier, and the search for a more accessible endpoint and a surrogate to os is being sought. Progression-free survival (pfs) is defined as time from randomization until first evidence of tumour progression or until death from any cause, whichever ABSTRACT