Myers K, Barrett A, Leach C, Matsuda T, Stevinson K, Lui C, Fu C, Bittoni M, Presley C. Understanding treatment preferences of patients with KRAS p.G12C[LC1] [MK2] – mutated advanced non-small cell lung cancer. Poster presented at the 2021 Virtual World Conference on Lung Cancer; September 8, 2021.

INTRODUCTION: Sotorasib, a novel, first-in-class, oral targeted therapy is in development for the treatment of KRAS p.G12C–mutated non-small cell lung cancer (NSCLC). The primary endpoint of sotorasib clinical studies reported to date has been objective response rate. Longer-term outcomes (e.g., overall survival) for sotorasib and patient preferences for treatment of KRAS p.G12C-mutated NSCLC are not currently available. Therefore, qualitative interviews were conducted with treatment-experienced patients with advanced KRAS p.G12C–mutated NSCLC to gain insight into: (a) patient experiences with treatment, (b) preferences for treatment attributes and benefit-risk profiles, and (c) willingness to accept uncertainty in longer-term treatment efficacy for a less toxic oral therapy in the second-line setting.

METHODS: Qualitative interviews were conducted with patients with locally advanced or metastatic KRAS p.G12C–mutated NSCLC who have undergone systemic therapy for NSCLC in the first-line setting. Twenty-four treatment-experienced, adult patients were recruited from the Ohio State University James Cancer Hospital. Of these, 17 participated in a single, 60-minute individual telephone interview using a semi-structured interview guide. Participants were asked to describe their experiences with NSCLC treatment, including benefits and side effects and their impact and importance, as well as to select their preference between two scenarios describing different combinations of treatment outcomes and toxicity profiles.

RESULTS: Among participants, mean (standard deviation) age was 63.6 (7.1) years, 12/17 (71%) were female, and 13/17 (76%) identified as white. All participants had received chemotherapy, and 8 (47%) had also received immunotherapy for advanced NSCLC. Ten participants (59%) reported experiencing multiple and/or severe toxicities from chemotherapy that significantly impacted their daily lives. Treatment toxicities associated with chemotherapy were fatigue (n = 16), hair loss (n = 12), nausea/vomiting (n = 10), weight change (n = 7), neuropathy (n = 7), change in appetite/taste of food (n = 7), gastrointestinal complications (n = 6), depression (n = 4), and mouth sores (n = 3). When asked to choose between an intravenous treatment with a benefit-risk profile similar to taxane-based chemotherapy and an oral treatment with a benefit-risk profile similar to sotorasib, the majority of participants (88.2%) chose an oral treatment with a hypothetical benefit-risk profile similar to that of sotorasib and indicated that they perceived a hypothetical 25% to 35% response rate to be meaningful despite an unknown survival benefit.

CONCLUSION: This was the first study to provide insight into the perspectives of patients with advanced KRAS p.G12C–mutated NSCLC. A range of experiences with NSCLC treatment was reported, and treatment-related preferences appeared to be somewhat dependent on previous treatment experience. Even without mature survival data, previously treated patients perceived a hypothetical 25% to 35% response rate of the oral therapy with a benefit-risk profile similar to sotorasib to be a meaningful benefit and favorable compared with the well-established survival expectations with taxane-based chemotherapy.

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