Owonikoko, Taofeek Kunle

e20608 Background: The American Society of Clinical Oncology recommends that physicians (MDs) assess the treatment goals and preferences of patients (pts) with advanced stage cancer. Available data, however, shows that pts’ values are not always well prioritized when making a treatment plan. Therefore, we iteratively developed a values tool containing 16 belief domains to inform MDs during conversations with their pts about the pts’ current priorities as they plan the next step in care. The purpose of this study was to determine the feasibility of using this values tool (defined as half of the tools having at least one value checked and half of the MDs discussing at least one value) in a phase I clinic setting. Methods: We audio-taped initial MD-pt conversations about potential enrollment in a phase I clinical trial at two academic medical centers (Emory and Mayo). The pts completed the values tool by selecting the 4 most important considerations for their next stage of care and were instructed to give the completed tool to the MD. The MDs were informed through the consent process but not specifically coached on use of the tool. The recorded conversations were coded using standard qualitative methodology to determine if a value from the tool was discussed. Results: There were 23 recorded encounters. All of the completed tools had at least one value checked and 19 of 23 (83%) completed tools were delivered to the MDs by the pts, as instructed. Of those who received the tool, 12 (63%) MDs discussed one or more of the values. The average satisfaction scores on a 5-point Likert scale were 3.9, 4.0, and 4.0, respectively, for tool clarity, ease of understanding, and benefit for pts who are offered a phase 1 trial (22/23 pts completed the evaluation). Average satisfaction scores from the 19 MDs who completed evaluations were 4.2 and 4.6, respectively, for influence of the tool on their treatment recommendation and accurate reflection of pts’ desires. Conclusions: The study met the predefined feasibility threshold and provides a strong rationale for future efficacy testing, including coaching of MDs. The tool was well accepted by both MDs and pts, and failure to deliver the completed tool by the pt was identified as a potential barrier to its effectiveness.

Abstract Lessons Learned Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials. Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC. Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. Background. Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. Methods. In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0–2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. Results. Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5–3.6) and 1.2 (95% CI, 1.1–1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2–7.6) and 3.4 (95% CI, 1.8–5.6) months for topotecan and linsitinib, respectively (p = .71). Grade 3/4 adverse events (>5% incidence) included anemia, thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine aminotransferase/aspartate aminotransferase elevations for linsitinib. Conclusion. Linsitinib was safe but showed no clinical activity in unselected, relapsed SCLC patients.