Prisma Health Cancer Institute, Greenville, South Carolina, USA.
Oncologist. 2021 Sep;26(9):e1499-e1507. doi: 10.1002/onco.13798. Epub 2021 May 8.
Disease control with signals of response were demonstrated, which should lead to future validating clinical trials using checkpoint inhibitors in this underserved rare malignancy population. Although the study of single types of rare cancers is practically challenging, clinical trial designs that aggregate such patients into cohorts treated similarly are feasible, even in the community setting.
Patients with rare cancers are an underserved population with limited access to clinical trials aside from phase I trials in the refractory setting. Treatment of these patients is often based on collections of anecdotes and small denominator review articles. Despite broad evidence of efficacy of combined immune checkpoint blockade across multiple tumor types, patients with rare tumors have not been afforded the opportunity for these therapies.
A phase II, investigator-initiated, single institution trial using durvalumab (1,500 mg every [Q]4 weeks × 13) and tremelimumab (75 mg Q4 weeks × 7, then Q12 weeks × 2) is reported. The population included 50 patients with advanced rare solid tumors (incidence <6/100,000 per year). The phase II dose and safety profile were defined in prior phase I trials. All patients had exhausted standard therapy options and all had received at least one prior line of systemic therapy (n = 49) unless a standard treatment option did not exist (n = 1).
A complete response was demonstrated in one patient with anal cancer. Striking partial responses were seen in four patients. Prolonged disease stability was noted in 18 patients. Thirteen patients experienced disease progression. Patients were considered unevaluable if unable to initiate therapy (n = 6) or unable to complete two cycles of therapy (n = 8). In all cases, patients were unevaluable because of clinical deterioration. The toxicity profile paralleled prior published studies. Toxicities were manageable and without new signals. There were two events of grade 4 immune-mediated hepatitis and one death from pneumonitis.
This single-cohort basket trial demonstrated clinical activity from combined checkpoint blockade in 23 of the 36 evaluable patients. Patients with rare cancers, not eligible for immunotherapy via conventional clinical trial mechanisms, should be considered for this therapy through compassionate use, further clinical trials, and national registry programs.
反应信号显示疾病得到控制，这应该会导致未来在这种服务不足的罕见恶性肿瘤人群中使用检查点抑制剂进行验证性临床试验。虽然研究单一类型的罕见癌症在实践上具有挑战性，但将此类患者聚集到接受类似治疗的队列中进行临床试验设计是可行的，即使在社区环境中也是如此。
罕见癌症患者是一个服务不足的人群，除了难治性疾病中进行的 I 期临床试验外，他们几乎无法获得临床试验的机会。这些患者的治疗通常基于轶事收集和小分母综述文章。尽管联合免疫检查点阻断在多种肿瘤类型中具有广泛的疗效证据，但罕见肿瘤患者没有机会接受这些治疗。
报告了一项由研究者发起的、单机构的 II 期临床试验，使用度伐单抗（每 4 周 1500 毫克×13 次）和 tremelimumab（每 4 周 75 毫克×7 次，然后每 12 周 2 次）。该人群包括 50 名晚期罕见实体肿瘤患者（发病率<6/100,000 人/年）。II 期剂量和安全性概况在之前的 I 期试验中确定。所有患者均已用尽标准治疗方案，且均接受过至少一线系统治疗（n=49），除非存在标准治疗方案（n=1）。
一名肛门癌患者出现完全缓解。四名患者出现显著部分缓解。18 名患者疾病稳定延长。13 名患者疾病进展。如果无法开始治疗（n=6）或无法完成两周期治疗（n=8），则患者被认为无法评估。在所有情况下，由于临床恶化，患者均无法评估。毒性概况与之前发表的研究相似。毒性可管理，无新信号。有两例 4 级免疫介导性肝炎和一例肺炎相关死亡。
这项单队列篮子试验显示，在 36 名可评估患者中的 23 名患者中，联合检查点阻断具有临床活性。不具备通过常规临床试验机制接受免疫治疗资格的罕见癌症患者应通过同情使用、进一步临床试验和国家登记计划考虑接受这种治疗。
