Abstract
8022 Background: The majority of actionable drivers in SQCLCs occur in the PI3K (30%) and FGFR1 (20%) pathways. The biologic behaviors and natural histories of these oncogenic subtypes are not well characterized. Methods: As of October 2011, all patients with SQCLCs at MSK have undergone prospective, multiplex testing of their FFPE tumors for FGFR1 amplification (FISH), PIK3CA mutations (Sequenom), PTEN loss (IHC), and PTEN mutations (exon sequencing), among others. Patient characteristics, outcomes, and metastatic sites were identified. Survival probabilities were estimated using the Kaplan-Meier method. Group comparisons were performed with log-rank tests and Cox proportional hazards methods. Results: 68 stage IV SQCLC patients were analyzed. 39 had tissue sufficient for next-gen sequencing. Genotypes were: FGFR1 amplified (16%); PTEN loss (24%), PIK3CA mutant (7%), PTEN mutant (13%). Events were non-overlapping save for 2 cases with PTENnonsense mutations and PTEN loss. The sole significant clinical difference (KPS, age, sex, lines of tx) was sex (women in PI3K group 52% vs. in others 23%, p=0.02). Metastatic patterns vs. other are shown in the Table. Median OS for PI3K vs. other: 10mo (95%CI:6.5-14.3) vs. 14mo (95%CI:9.6-36.7), p=0.02. Median OS for FGFR1 vs. others: 19mo (95%CI:9-NR) vs. 10mo (95%CI:6.5-14.3), p=0.3. Multivariate analysis for OS: PI3K vs. other, HR death=2.3 (95%CI:1.1-4.8, p=0.03); Age ≥65, HR=1.3 (95%CI:0.6-2.9, p=0.6); KPS≥70, HR=0.5 (95%CI:0.2-1.7, p=0.3); Male sex, HR=0.7 (95%CI:0.3-1.4, p=0.3). Conclusions: Patients with stage IV PI3K-aberrant SQCLCs have poorer survival compared to other patients with SQCLCs. Brain metastases occurred exclusively in patients with PI3K-aberrant tumors. These data suggest that PI3K pathway activation confers a distinct biology, and that targeting this in SQCLC patients with brain metastases may be an effective therapeutic strategy. [Table: see text]
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