Core values of patients with advanced cancer considering participation in an early-phase clinical trial: a qualitative study

Objective: This article identifies the core values that play a role in patients’ decision-making process about participation in early-phase clinical cancer trials. Methods: Face-to-face, semi-structured serial interviews (n = 22) were performed with thirteen patients with advanced cancer recruited in two Dutch specialized cancer centers. In a cyclic qualitative analysis process, open and axial coding of the interviews finally led to an overview of the values that are woven into patients’ common language about cancer and clinical trials. Results: Six core values were described, namely, acceptance creates room for reconsideration of values, reconciliation with one’s fate, hope, autonomy, body preservation, and altruism. Previously found values in advanced cancer, such as acceptance, hope, autonomy, and altruism, were further qualified. Reconciliation with one’s fate and body preservation were highlighted as new insights for early-phase clinical cancer trial literature. Conclusions: This article furthers the understanding of core values that play a role in the lives and decision-making of patients with advanced cancer who explore participation in early-phase clinical cancer trials. These values do not necessarily have to be compatible with one another, making tragic choices necessary. Understanding the role of core values can contribute to professional sensitivity regarding what motivates patients’ emotions, thoughts, and decisions and help patients reflect on and give words to their values and preferences. It supports mutual understanding and dialog from which patients can make decisions according to their perspectives on a good life for themselves and their fellows in the context of participation in an early-phase clinical cancer trial

Phase I study of lapatinib plus trametinib in patients with KRAS-mutant colorectal, non-small cell lung, and pancreatic cancer

PURPOSE: KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). METHODS: Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. RESULTS: Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. CONCLUSION: Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated