A Population Survival Kinetics Assessment of Extensive Small Cell Lung Cancer and Rationale for Maintenance Therapy

Progression-free survival (PFS) and overall survival (OS) curves generally approximate first-order kinetics. On log-linear plots, convex curves with downward inflection (indicating late acceleration of progression/death) might arise from stopping effective therapies. We digitized published PFS/OS curves for etoposide/platinum-treated extensive small-cell lung cancer (SCLC) and other malignancies and replotted the curves log-linearly. Of 26 SCLC PFS curves, 21 (81%) were highly convex (with a marked late down-turn), and 26 (100%) were moderately or highly convex vs. 35/888 (4%) highly convex and 186 (21%) moderately/highly convex curves for other cancers (<i>p</i> < 0.0001). For SCLC, all 32 OS curves were moderately or highly convex vs. 87/363 (24%) that were moderately/highly convex for other cancers (<i>p</i> < 0.0001). The SCLC PFS curves had an initial downward inflection at a median of 3.1 months (around the completion of first-line chemotherapy), then a second inflection at 5.4 months, with further acceleration of progression. The median PFS half-life was 11.9 months while receiving treatment vs. 1.7 months after the second inflection point. Immunotherapy benefit appeared to be limited to 6-10% of the population. SCLC PFS/OS curves are more often convex than for other cancers, reflecting SCLC chemotherapy sensitivity but rapid progression following the completion of first-line chemotherapy. Effective maintenance strategies are needed.