In the CodeBreaK 200 phase 3 trial, sotorasib significantly improved PFS (primary endpoint) versus docetaxel in previously treated KRASG12C-mutated NSCLC. Previously described patient-reported outcomes (PROs) favored sotorasib over docetaxel for global health status, physical functioning, dyspnea, and cough (ESMO 2022, LBA10). Here, we report the severity and impact of symptoms on patients’ quality of life (QOL) in response to treatment.
In this trial, 345 patients who progressed after receiving platinum-based chemotherapy and a checkpoint inhibitor were randomized 1:1 to receive sotorasib (960 mg orally QD) or docetaxel (75 mg/m2 intravenously Q3W). Well-established, validated questionnaires captured patients’ perception of their QOL and symptom burden: EuroQOL-5 Dimension Visual Analogue Scale (EQ-5D VAS), PRO-Common Terminology Criteria for Adverse Events (CTCAE), Brief Pain Inventory (BPI), and question GP5 from the Functional Assessment of Cancer Therapy Tool General form (FACT-G). For ordinal outcomes, change from baseline to week 12 was assessed with generalized estimating equations.
Compared with patients receiving sotorasib, those receiving docetaxel were more severely bothered by their side effects (odds ratio [OR] 5.71) and experienced symptoms at a higher severity (pain: OR 2.94, aching muscles: OR 4.40, aching joints: OR 4.17, mouth or throat sores: OR 4.26). Further their symptoms more strongly interfered with their usual/daily activities (pain: OR 3.18, aching muscles: OR 3.90, aching joints: OR 10.68). QOL worsened five days after initial docetaxel treatment while remaining stable with sotorasib (change from baseline in VAS score: –8.4 vs 1.5). The VAS showed a long-term worsening of QOL with docetaxel while the VAS remained stable with sotorasib (–5.8 vs 2.2 at week 12).
Patients treated with sotorasib reported less severe symptoms than those treated with docetaxel; hence, their daily lives were positively affected. In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel suggesting that sotorasib may be a more tolerable treatment option for patients with pretreated, KRASG12C-mutated advanced NSCLC.
NCT04303780
Medical writing support provided by Dr. Kristina Y. Aguilera (Ph.D.), Amgen Inc.