Progression-free Survival Decreases with Each Subsequent Therapy in Patients Presenting for Phase I Clinical Trials

Abstract

Background: There is often a finite progression-free interval of time between one systemic therapy and the next when treating patients with advanced cancer. While it appears that progression-free survival (PFS) between systemic therapies tends to get shorter for a number of factors, there has not been a formal evaluation of diverse tumor types in an advanced cancer population treated with commercially-available systemic therapies.

Methods: In an attempt to clarify the relationship between PFS between subsequent systemic therapies, we analyzed the records of 165 advanced cancer patients coming to our clinic for consideration for participation in six different phase I clinical trials requiring detailed and extensive past medical treatment history documentation.

Results: There were 77 men and 65 women meeting inclusion criteria with a median age at diagnosis of 55.3 years (range 9.4-81.6). The most common cancer types were colorectal (13.9%), other gastrointestinal (11.8%), prostate (11.8%). A median of 3 (range 1-11) systemic therapies were received prior to phase I evaluation. There was a significant decrease in PFS in systemic therapy for advanced disease from treatment 1 to treatment 2 to treatment 3 (p = 0.002), as well as, from treatment 1 through treatment 5 (p < 0.001).

Conclusions: In an advanced cancer population of diverse tumor types, we observe a statistically significant decrease in PFS with each successive standard therapy. Identification of new therapies that reverse this trend of decreasing PFS may lead to improved clinical outcomes.

Keywords: Progression-free survival; advanced cancer; chemotherapy; phase I clinical trials; systemic therapy.

Figure 1

PFS in days from first systemic therapy to third systemic therapy. Boxplot detail showing significant decrease in PFS calculated for first systemic therapy (TX1), second systemic therapy (TX2), and third systemic therapy (TX3) in days.

Figure 2

PFS in days from first systemic therapy to fifth systemic therapy. Boxplot detail showing significant decrease in PFS calculated for first systemic therapy (TX1), second systemic therapy (TX2), third systemic therapy (TX3), fourth systemic therapy (TX4), and fifth systemic therapy (TX5) in days.