Outcomes of patients with advanced non-small cell lung cancer treated in a phase I clinic

Abstract

Background: The outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated in phase I clinical trials have not been systematically analyzed.

Methods: We reviewed the records of consecutive patients with advanced/metastatic NSCLC who were treated in the Phase I Clinical Trials Program at MD Anderson from August 2004 to May 2009.

Results: Eighty-five patients (51 men, 34 women) treated on various phase I protocols were identified. The median age was 62 years (range, 30-85). The median number of previous systemic therapies was two (range, 0-5). A partial response was observed in eight patients (9.5%) and stable disease lasting >4 months was observed in 16 patients (19%). The median overall survival time was 10.6 months and median progression-free survival (PFS) time was 2.8 months, which was 0.6 months shorter than the median PFS of 3.4 months following prior second-line therapy. Factors predicting longer survival in the univariate analysis were an Eastern Cooperative Oncology Group performance status (PS) score of 0-1, no prior smoking, two or fewer organ systems involved, a hemoglobin level ≥ 12 g/dL, liver metastases, a history of thromboembolism, and a platelets count > 440 × 10(9)/L. In the multivariate analysis, a PS score of 0-1 and history negative for smoking predicted longer survival. Sixty-two (73%) patients had grade ≤ 2 toxicity, and there were no treatment-related deaths.

Conclusion: Phase I clinical trials were well tolerated by selected patients with advanced NSCLC treated at M.D. Anderson. Nonsmokers and patients with a good PS survived longer. PFS in our population was shorter in smokers/ex-smokers and patients with a PS score of 2. It is reasonable to refer pretreated patients with a good PS to phase I clinical trials.

Figure 1.

Waterfall plot of patients with non-small cell lung cancer treated in phase I clinical trials. Twenty-six (31%) patients had some tumor shrinkage, including eight partial responses (9.5%). Patients treated with a combination of targeted therapy and chemotherapy (green bars) were most likely to respond (5 of 13, 38.5%). Abbreviations: PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.

Figure 2.

Kaplan–Meier estimates of OS. (A): The median OS time in phase I trials was 10.6 months (95% CI, 8.9–14.7 months). (B): Patients with an ECOG PS score of 0–1 had a longer OS time than patients with an ECOG PS score of 2—11.6 months (95% CI, 8.7–14.4 months) versus 2.9 months (95% CI, 1.9–3.9 months) (p = .0008). (C): Nonsmokers had a longer OS time than smokers and ex-smokers—19.9 months (95% CI, 10.2–27.8 months) versus 9 months (95% CI, 7.9–10.1 months) (p = .007). Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OS, overall survival; PS, performance status.

Figure 3.

Kaplan–Meier estimates of PFS. PFS on first-line systemic therapy (blue), second-line systemic therapy (orange), and phase I therapy (red). The median PFS time on first-line treatment was significantly longer than the median PFS time on phase I treatment (p < .0001). The median PFS time on second-line treatment was longer than the median PFS time on phase I treatment and at borderline statistical significance (p = .05). Abbreviations: CI, confidence interval; PFS, progression-free survival.