Effect of prior cancer on outcomes in advanced lung cancer: implications for clinical trial eligibility and accrual

Abstract

Background: Prior cancer is a common exclusion criterion in lung cancer trials. This practice reflects concerns that prior cancer may affect trial conduct or outcomes. However, the impact of prior cancer on survival in lung cancer is not known.

Methods: We identified patients older than age 65 years with stage IV lung cancer diagnosed between 1992 and 2009 in the Surveillance, Epidemiology, and End Results-Medicare linked registry. Prior cancer was characterized by type, stage, and timing. All-cause and lung cancer-specific survival were compared between patients with and without prior cancer using propensity score-adjusted Cox regression.

Results: Overall, 102 929 patients with stage IV lung cancer were identified, of whom 14.7% had a history of prior cancer. More than two-thirds (76.0%) of prior cancers were localized or regional stage; most were diagnosed five or fewer years prior to the lung cancer diagnosis. In propensity score-adjusted analysis, patients with prior cancer had better all-cause (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.91 to 0.94) and lung cancer-specific (HR = 0.81, 95% CI = 0.79 to 0.82) survival. In a simulated clinical trial-eligible population (age <75 years, no comorbidity, treated with chemotherapy), similar trends were noted. In subset analyses according to stage, type, and timing of prior cancer, no group of patients with prior cancer had inferior survival compared with patients without prior cancer.

Conclusion: Among patients with stage IV lung cancer, prior cancer does not convey an adverse effect on clinical outcomes, regardless of prior cancer stage, type, or timing. Broader inclusion in clinical trials of advanced lung cancer patients with a history of prior cancer should be considered.

Figure 1.

Type (A), stage (B), and timing (C) of the most recent prior cancers. Cell sizes less than 11 are suppressed per the Surveillance, Epidemiology, and End Results–Medicare data use agreement; Denominators are not equal because of missing data. All statistical tests were two-sided.

Figure 2.

All-cause (A) and lung cancer–specific (B) survival for patients with and without any prior malignancy. All statistical tests were two-sided.

Figure 3.

Overall survival according to type (A), stage (B), and timing (C) of prior cancer diagnosis. “Other” denotes patients with no prior malignancy or a history of prior malignancy diagnosed outside the referenced time frame. All statistical tests were two-sided.