Durvalumab加化疗，联合或不联合Tremelimumab作为转移性非小细胞肺癌的一线治疗

SCI

19 November 2022

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study

(J Clin Oncol ;IF:50.717)

CORRESPONDENCE TO: Melissa L. Johnson, MD, Sarah Cannon Research Institute—Tennessee Oncology, 250 25th Ave North, Suite 100, Nashville, TN 37203; e-mail: mjohnson@tnonc.com

PURPOSE 目的

The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D +CT) and durvalumab plus chemotherapy (D+CT) versus chemotherapy alone (CT) in firstline metastatic non–small-cell lung cancer (mNSCLC).

开放标签的3期POSEIDON研究在转移性非小细胞肺癌(mNSCLC)一线治疗中评估了tremelimumab + durvalumab和化疗(T + D+CT)以及durvalumab +化疗(D+CT)与单独化疗(CT)的疗效。

METHODS 方法

Patients (n=1,013) with EGFR/ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D+CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT.

EGFR/ALK野生型mNSCLC患者(n=1,013)被随机分组(1∶1∶1)，接受tremelimumab 75 mg + durvalumab 1,500 mg和铂类化疗，最长4个周期，21日为1个周期，之后每4周1次durvalumab治疗，直至疾病进展，并接受1次额外tremelimumab剂量。Durvalumab +化疗最多4个周期，每个周期21日，之后每4周1次Durvalumab，直至疾病进展；或长达6个21天周期的化疗(联用或不联用培美曲塞维持治疗)。主要终点是D+CT组与CT组相比的无进展生存期(PFS)和总生存期(OS)。次要终点是T + D + CT与CT相比的PFS和OS。

RESULTS 结果

PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P= .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95%CI, 0.65 to 0.92; P= .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D+ CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events.

与常规治疗相比，D + CT治疗显著改善了PFS(风险比0.74;95% CI, 0.62 ~ 0.89;P = 0.0009;中位时间分别为5.5个月和4.8个月);OS改善程度未达到统计学显著性(风险比，0.86;95% CI, 0.72 ~ 1.02;P = 0.0758;中位时间13.3个月 VS 11.7个月;24个月OS分别为29.6%和22.1%)。PFS (HR, 0.72;95% CI, 0.60 ~ 0.86;P = .0003;中位时间，6.2个月vs . 4.8个月)和OS(风险比，0.77;95%CI, 0.65 ~ 0.92;P = .0030;中位随访时间14.0个月和11.7个月;24个月OS分别为32.9%和22.1%)显著改善。T + D + CT组、D + CT组和CT组的3 ~ 4级不良事件发生率分别为51.8%、44.6%和44.4%;分别有15.5%、14.1%和9.9%的患者因治疗相关不良事件停止治疗。

Conclusions 结论

D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.

与CT相比，D + CT显著改善了PFS。与CT相比，在durvalumab和化疗的基础上加用有限疗程的tremelimumab显著改善了OS和PFS，且未增加耐受负担，这提供了一线mNSCLC的潜在新选择。