Hospital de Clínicas de Porto Alegre, Unidade de Pesquisa Clinica em Oncologia, Porto Alegre, Brazil.
Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Pigment Cell Melanoma Res. 2021 Sep;34(5):973-977. doi: 10.1111/pcmr.12960. Epub 2021 Feb 15.
Anti-programmed death-1 agents are an established option for advanced melanoma, but the anti-programmed death-ligand 1 (anti-PD-L1) antibody atezolizumab, an agent approved for the treatment of multiple solid tumors, was not previously evaluated. This phase 1b study cohort (NCT03178851; cohort C) evaluated first-line atezolizumab 1,200 mg every 3 weeks in adults with BRAF wild-type, histologically confirmed, advanced or metastatic melanoma. The co-primary end points were confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1 and disease control rate (DCR = complete response [CR] +partial response [PR] +stable disease [SD] at 16 weeks). Of 52 enrolled patients, most had lactate dehydrogenase levels lower than the upper limit of normal (77%) and PD-L1-positive tumors (55%). Investigator-assessed confirmed ORR was 35% (95% CI, 22%-49%) and included three CRs (6%) and 15 PRs (29%); DCR was 46%. Median investigator-assessed progression-free survival was 3.7 months (95% CI, 2.1-7.3). The most common any-grade adverse events were anemia (27%), headache (19%), hypertension (19%), constipation (17%), diarrhea (17%), hypothyroidism (17%), asthenia (15%), and pain in extremity (15%). First-line atezolizumab monotherapy is safe and tolerable and has antitumor activity in patients with BRAF wild-type advanced or metastatic melanoma.
抗程序性死亡-1 药物是晚期黑色素瘤的标准治疗选择，但抗程序性死亡配体 1（抗 PD-L1）抗体阿替利珠单抗已被批准用于多种实体瘤的治疗，此前尚未对此药进行评估。这项 1b 期研究队列（NCT03178851；队列 C）评估了一线阿替利珠单抗 1200mg，每 3 周给药一次，用于治疗 BRAF 野生型、组织学确认的晚期或转移性黑色素瘤的成人患者。主要共同终点是根据实体瘤反应评价标准 1.1（RECIST v1.1）评估的确认客观缓解率（ORR）和疾病控制率（DCR=完全缓解[CR]+部分缓解[PR]+疾病稳定[SD]在 16 周时）。在 52 名入组患者中，大多数患者的乳酸脱氢酶水平低于正常值上限（77%），且肿瘤 PD-L1 阳性（55%）。研究者评估的确认 ORR 为 35%（95%CI，22%-49%），包括 3 例 CR（6%）和 15 例 PR（29%）；DCR 为 46%。研究者评估的中位无进展生存期为 3.7 个月（95%CI，2.1-7.3）。最常见的任何级别不良事件为贫血（27%）、头痛（19%）、高血压（19%）、便秘（17%）、腹泻（17%）、甲状腺功能减退症（17%）、乏力（15%）和四肢疼痛（15%）。一线阿替利珠单抗单药治疗安全且耐受良好，并且在 BRAF 野生型晚期或转移性黑色素瘤患者中具有抗肿瘤活性。
