Medical Oncology Department, Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), UVic-UCC, IOB-Quirón, Passeig de la Vall d'Hebron 119-129, Barcelona, 08035, Spain.
IDOR, Hospital Vila Nova Star, Rede D'Or-Sao Luiz, Sao Paulo, Brazil.
Gastric Cancer. 2023 Jan;26(1):123-131. doi: 10.1007/s10120-022-01335-4. Epub 2022 Sep 6.
Dual-targeted anti-HER2 therapy significantly improves outcomes in HER2-positive breast cancer and could be beneficial in other HER2-positive cancers. JACOB's end-of study analyses aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy for previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer.
Eligible patients were randomized 1:1 to pertuzumab/placebo plus trastuzumab and chemotherapy every 3 weeks.
overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety.
The intention-to-treat population comprised 388 patients in the pertuzumab arm and 392 in the placebo arm. The safety population comprised 385 and 388 patients, respectively. Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72-0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62-0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment. There was a trend for more favorable hazard ratios in certain subgroups related to HER2 amplification/overexpression. Safety was comparable between arms, except for serious and grade 3-5 adverse events, and any-grade diarrhea, which were more frequent with pertuzumab.
JACOB did not meet its primary endpoint. Nonetheless, the study continues to demonstrate some, albeit limited, evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up. Trial registration NCT01774786; https://clinicaltrials.gov/ct2/show/NCT01774786 .
双重靶向抗 HER2 治疗显著改善了 HER2 阳性乳腺癌患者的预后，并且可能对其他 HER2 阳性癌症有益。JACOB 的研究结束时的分析旨在评估曲妥珠单抗联合帕妥珠单抗和化疗在未经治疗的 HER2 阳性转移性胃或胃食管交界处癌患者中的长期疗效和安全性。
符合条件的患者按 1:1 比例随机分配至曲妥珠单抗/安慰剂联合帕妥珠单抗和每 3 周一次的化疗。
总生存期（OS）。次要终点包括无进展生存期（PFS）、客观缓解率（ORR）、缓解持续时间（DoR）和安全性。
意向治疗人群中，曲妥珠单抗组和安慰剂组分别有 388 例和 392 例患者。安全性人群分别包括 385 例和 388 例患者。中位随访时间≥44.4 个月。与安慰剂组相比，曲妥珠单抗组的中位 OS 延长了 3.9 个月（风险比 0.85 [95%置信区间，0.72-0.99]），中位 PFS 延长了 1.3 个月（风险比 0.73 [95%置信区间，0.62-0.85]）。ORR 略高（57.0% vs. 48.6%），且曲妥珠单抗治疗的中位 DoR 延长了 1.8 个月。在与 HER2 扩增/过表达相关的某些亚组中，具有更有利的风险比的趋势。除严重和 3-5 级不良事件以及任何级别腹泻外，两组之间的安全性相当，这些不良事件在曲妥珠单抗组更为常见。
JACOB 没有达到其主要终点。尽管如此，该研究在长期随访后继续证明了一些，尽管有限，在未经治疗的 HER2 阳性转移性胃或胃食管交界处癌患者中，曲妥珠单抗联合帕妥珠单抗和化疗具有一定的治疗活性和可接受的安全性。试验注册 NCT01774786；https://clinicaltrials.gov/ct2/show/NCT01774786。
