Pharmerit - an OPEN Health Company, Bethesda.
Pfizer, Inc, New York, New York.
Cancer. 2020 Oct 1;126(19):4315-4321. doi: 10.1002/cncr.33072. Epub 2020 Jul 22.
In a randomized study, glasdegib (a hedgehog inhibitor) plus low-dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) approach was used to evaluate comparative quality-adjusted survival.
Overall survival was partitioned into the following: time with any treatment-emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q-TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility-adjusted time.
At 20 months of follow-up, the survival probabilities for the glasdegib-LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib-LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8-5.2 months) and TOX (+0.8 months; 95% CI, 0.1-1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, -1.9 to 2.3 months). Q-TWiST was 4.0 months (95% CI, 2.1-5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality-adjusted survival with respect to LDAC. Results were robust to the length of follow-up (6-24 months) and remained significant when all adverse events, regardless of grade, were included.
These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively "good" health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option.
在一项随机研究中，与低剂量阿糖胞苷（LDAC）相比，吉西他滨（一种 Hedgehog 抑制剂）联合 LDAC 显著延长了急性髓系白血病（AML）患者的总生存期。采用无疾病进展或毒性症状的质量调整时间（Q-TWiST）方法评估比较性质量调整生存。
总生存期分为以下几部分：出现任何 3 级或更高等级不良事件（TOX）的时间；无疾病进展或毒性症状的时间（TWiST）；以及因临床反应不足、复发或疾病进展后停药的时间（REL）。通过将每个状态的受限平均时间乘以各自的效用，然后将效用调整后的时间相加来计算 Q-TWiST。
在 20 个月的随访中，吉西他滨-LDAC 组和 LDAC 组的生存率分别为 28.2%和 7.9%。与 LDAC 组（n=38）相比，吉西他滨-LDAC 组（n=78）患者的 TWiST 显著延长（+3.4 个月；95%置信区间[CI]，1.8-5.2 个月）和 TOX（+0.8 个月；95%CI，0.1-1.6 个月），但 REL 延长但无统计学意义（+0.3 个月；95%CI，-1.9 至 2.3 个月）。吉西他滨联合 LDAC 组的 Q-TWiST 延长了 4.0 个月（95%CI，2.1-5.8 个月），这意味着相对于 LDAC，吉西他滨联合 LDAC 可使质量调整生存提高 75%。这些结果在 6-24 个月的随访期内是稳健的，并且当包括所有不良事件（无论等级如何）时，结果仍然显著。
这些结果表明，吉西他滨联合 LDAC 与单独使用 LDAC 相比，生存获益的大部分是 TWiST，这代表了在相对“良好”健康状况下的额外时间。这些结果支持吉西他滨联合 LDAC 作为不适合强化化疗的 AML 患者初始治疗的临床价值。
