Patient-reported outcomes from the CodeBreaK 200 trial favour sotorasib over docetaxel
In addition to improving clinical efficacy outcomes, sotorasib maintains quality of life (QoL) versus docetaxel in patients with pre-treated KRASG12C-mutated advanced non-small cell lung cancer (NSCLC) enrolled in the CodeBreak 200 trial. Compared with patients receiving sotorasib, those receiving docetaxel were more severely bothered by their side effects and their symptoms more strongly interfered with their daily activities.
Sotorasib is a first-in-class KRASG12C inhibitor that is approved for patients with previously treated KRASG12C-mutated advanced non-small cell lung cancer (NSCLC). In the phase III CodeBreak 200 study, the primary endpoint of progression-free survival (PFS) was significantly improved with sotorasib vs. docetaxel. In addition, also objective response rate (ORR), disease control rate (DCR), time to response (TTR) and duration of response (DOR) were in favour of sotorasib but there was no difference in overall survival (OS). Finally, previously described prespecified patient-reported outcomes (PROs) favoured sotorasib over docetaxel for global health status, physical functioning, dyspnoea and cough. Now, additional PROs relating to quality of life (QoL) and symptom severity were reported.
Study design
CodeBreak 200 enrolled patients with locally advanced/unresectable or metastatic KRASG12C-mutated NSCLC who received at least one prior treatment, including platinum-based chemotherapy and a checkpoint inhibitor. Patients were not allowed to have active brain metastases and must have an ECOG performance status ≤1. In total, 345 patients were randomised in a 1:1 ratio to sotorasib (960 mg oral daily) or docetaxel (75 mg/m2 IV once every three weeks). As secondary and exploratory endpoints, patients completed well-established, validated PRO questionnaires to capture the 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). The change over time for PROs was assessed at baseline (cycle 1 day 1) until treatment discontinuation. PROs were measured on day one of each cycle and randomisation stratification factors were used for adjustment.
Results
As previously reported, general baseline characteristics were comparable between the treatment groups. PRO measures at baseline were comparable between the sotorasib and docetaxel groups, including the severity, frequency, and onset of symptoms. 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). In addition, their symptoms more strongly interfered with their usual/daily activities (pain: OR 3.18, aching muscles: OR 3.90, aching joints: OR 10.68). Furthermore, QoL worsened five days after initial docetaxel treatment while remaining stable with sotorasib (change from baseline in visual analogue score [VAS]: –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). Finally, patient mobility, self-care and usual activities were all improved in the sotorasib group at week 12.
Conclusion
In the phase III, global, randomised CodeBreak 200 study, primary and secondary endpoints were improved for sotorasib vs. docetaxel, without an improvement in OS. In the PRO analyses, patients treated with sotorasib vs. docetaxel were less bothered by their side effects, experienced less symptom severity, less interference in daily activities and a similar symptom frequency. In addition, sotorasib-treated patients had improved mobility, self-care and ability to perform usual activities. These results suggest that sotorasib is a more tolerable treatment option for patients with pre-treated, KRASG12C-mutated advanced NSCLC.
Reference
Waterhouse D, et al. Patient-reported outcomes from the CodeBreaK 200 phase 3 trial comparing sotorasib versus docetaxel in KRAS G12C-mutated NSCLC. Presented at ELCC 2023; Abstract 4O.
