Lehigh Valley Health Network, Allentown, PA.
University of Texas MD Anderson Cancer Center, Houston, TX.
JCO Precis Oncol. 2022 Oct;6:e2200306. doi: 10.1200/PO.22.00306.
The TAPUR Study is a pragmatic phase II basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from two cohorts of patients with colorectal cancer (CRC) with either amplifications or or mutations treated with pertuzumab plus trastuzumab (P + T) are reported.
Eligible patients with measurable CRC were selected for treatment with P + T according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary study end point of disease control (DC; objective response [OR] or stable disease of at least 16 weeks duration [SD16+]). Secondary end points include safety, response duration, progression-free survival (PFS), and overall survival (OS).
Thirty-eight patients with CRC with amplification (N = 28) or / mutations (N = 10) were treated with P + T. For the amplification cohort, DC and OR were observed in 54% and 25% of patients, respectively; the median PFS and median OS (95% CIs) were 17.2 (11.1 to 27.4) weeks and 60.0 (32.1 to 102.3) weeks, respectively. For the / mutation cohort, DC and OR were observed in 10% and 0% of patients, respectively; the median PFS and median OS were 9.6 (5.1 to 16.0) weeks and 28.8 (7.6 to 146.3) weeks, respectively. Four of 38 patients experienced grade 3 adverse events or serious adverse events including anemia, infusion reaction, diarrhea, left ventricular systolic dysfunction, and decreased lymphocyte count.
Although P + T treatment does not appear to have antitumor activity in CRC with mutations, this combination has antitumor activity in patients with CRC with amplification and warrants further study.
TAPUR 研究是一项实用的 II 期篮子试验，评估了商业上可获得的靶向药物在携带潜在可操作基因组改变的晚期癌症患者中的抗肿瘤活性。报告了接受曲妥珠单抗联合帕妥珠单抗（P + T）治疗的具有结直肠癌（CRC）扩增或 / 或 / 突变的两个患者队列的数据。
根据方案规定的基因组匹配规则，选择可测量的 CRC 患者接受 P + T 治疗。患者无其他标准治疗选择，东部合作肿瘤学组表现状态 0-2，器官功能良好。采用西蒙两阶段设计，主要研究终点为疾病控制（DC；客观缓解[OR]或至少 16 周持续稳定疾病[SD16+]）。次要终点包括安全性、反应持续时间、无进展生存期（PFS）和总生存期（OS）。
38 例具有扩增（N = 28）或 / 突变（N = 10）的 CRC 患者接受了 P + T 治疗。对于扩增队列，DC 和 OR 分别在 54%和 25%的患者中观察到；中位 PFS 和中位 OS（95%CI）分别为 17.2（11.1 至 27.4）周和 60.0（32.1 至 102.3）周。对于 / 突变队列，DC 和 OR 分别在 10%和 0%的患者中观察到；中位 PFS 和中位 OS 分别为 9.6（5.1 至 16.0）周和 28.8（7.6 至 146.3）周。38 例患者中有 4 例发生 3 级不良事件或严重不良事件，包括贫血、输注反应、腹泻、左心室收缩功能障碍和淋巴细胞计数减少。
尽管 P + T 治疗似乎对 CRC 中的 / 突变没有抗肿瘤活性，但该联合疗法对具有扩增的 CRC 患者具有抗肿瘤活性，值得进一步研究。
