A sub-group analysis from the ENDEAVOR study: health-related quality of life in relapsed/refractory multiple myeloma

The results of the prospective, open-label, multi-center randomized phase III ENDEAVOR trial (NCT01568866) illustrated that the combination of carfilzomib and dexamethasone (Kd56) had superior progression-free survival (PFS) compared with bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM).¹ The development in therapies have improved survival outcomes for patients with MM, however advances to health-related quality of life (HR-QoL) have been limited.² The results from the exploratory endpoint, HR-QoL, from the ENDEAVOR study was published in Blood Cancer Journal, by Professor Heinz Ludwig, a member of our Steering Committee, and colleagues.³

Patients and methods

• N = 929 patients with RRMM were randomized
• Patients randomized 1:1 to receive either Kd56 or Vd
• Patients in the Kd56 arm (n = 464) received carfilzomib (IV; 20 mg/m²; days 1, 2 of cycle 1; then 56 mg/m² on days 1, 2, 8, 9, 15, and 16 of 28-day cycle) combined with dexamethasone (oral/IV; 20 mg; days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycle)
• Patients in the Vd arm (n = 465) received bortezomib (IV/subcutaneous; 1.3 mg/m²; days 1, 4, 8, and 11 of 21-day cycle) in combination with dexamethasone (oral/IV; 20 mg; days 1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycle)
• Assessment of patient-reported outcomes (PROs) occurred using:
  • The European Organisation for Research and Treatment of Cancer QoL questionnaire (QLQ-C30) to assess HR-QoL
  • The MM-specific module (QLwQ-MY20) to assess disease specific myeloma parameters
  • The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity (FACT-GOG-Ntx) “Additional Concerns” neurotoxicity subscale to assess neurotoxicity
  • Patients included in the PRO analysis following at least one post-baseline PRO assessment before end of treatment: 911 (Kd56, n = 459; Vd, n = 452)

Key findings

All data shown as Kd56 group versus Vd group, where applicable

• Median duration on study treatment: 40 weeks vs 27 weeks
• Significantly higher HR-QoL scores in the Kd56 group compared to the Vd group, P < 0.0001
• Overall treatment difference point estimate: 3.5 (95% CI, 2.0–5.1)
• Estimated overall treatment effect: 4.4 (95% CI, 2.8–6.0; P < 0.0001)
• Dropout seemingly not associated with the rate of change in PRO scores over time
• Patients in the Kd56 group showed significant benefits compared to patients in the Vd group, with regards to fatigue (P = 0.04), pain (P = 0.02), side effects (P < 0.0001) and neurotoxicity (P = 0.0002)
• At week 12, patients achieving at least a 15-point improvement: 21.4% vs 16.1%, P = 0.0658
• Time to deterioration in HR-QoL was longer in the Kd56 group: HR = 0.77 (95% CI, 0.65–0.92), P = 0.0046
• Patients achieving a partial response (PR) or better: 316 vs 251
  • For treatment responders, proportion of patients with maintained or improved HR-QoL scores from baseline: 55–74% vs 47–58%
  • For treatment non-responders, the proportion of patients with maintained or improved HR-QoL scores from baseline: 43–100% vs 0–100%

The study authors concluded that the goal of MM therapy includes disease control and improved outcomes, although treatment should occur in the knowledge that HR-QoL is also maintained or improved for patients. The ENDEAVOR study demonstrated significant superiority in the Kd56 regimen compared to the Vd regimen in terms of PFS. From this sub-group analysis, Professor Heinz Ludwig and colleagues showed a declining trend in HR-QoL in both study arms, with the results highlighting a statistical, but not clinical, difference between the groups in terms of the QLQ-C30 assessment. The study investigators outlined that the Kd56 regimen should be considered for patients with RRMM, although careful consideration is needed to assess the impact of both the disease and treatment on HR-QoL.