Bongiovanni Alberto, Nicolini Silvia, Ibrahim Toni, Foca Flavia, Sansovini Maddalena, Di Paolo Arianna, Grassi Ilaria, Liverani Chiara, Calabrese Chiara, Ranallo Nicoletta, Matteucci Federica, Paganelli Giovanni, Severi Stefano
Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Cancers (Basel). 2022 Dec 7;14(24):6022. doi: 10.3390/cancers14246022.
Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome.
A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed.
Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2-63.2) median PFS was 33.0 months (95%CI: 27.1-48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1-94.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2-98.0) vs. 40.0% (95%CI: 6.6-73.4), respectively. A total of 233 adverse events were recorded. Grade 1-2 hematological toxicity was the most frequent.
The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS.
神经内分泌肿瘤（NETs）是一种预后各异的罕见恶性肿瘤。至少25%的转移性患者患有功能性神经内分泌肿瘤（F-NETs），可分泌生物活性肽，导致特定的衰弱性症状，偶尔还会出现危及生命的症状，如腹泻和潮红。生长抑素类似物（SSAs）通常有效，但除此之外几乎没有其他治疗选择。我们评估了177 Lu-DOTATATE对进展性转移性F-NETs和SSA难治性综合征患者的临床疗效。
对参加转移性NETs II期临床试验的患者进行了一项非预先计划的联合分析。我们将来自具有≥1种对奥曲肽难治的体征/症状且≥1个可测量病灶的F-NET患者的数据进行了外推。分析了综合征反应（SR）、总生存期（OS）、无进展生存期（PFS）、耐受性和疾病反应。
共纳入68例患者，大多数（88.1%）有综合征反应。根据RECIST标准，1例（1.5%）患者达到完全缓解（CR），21例（32.3%）部分缓解（PR），40例（61.5%）疾病稳定（SD）。中位随访28.9个月（范围2.2 - 63.2个月），中位PFS为33.0个月（95%置信区间：27.1 - 48.2）。分析时中位总生存期（mOS）尚未达到；2年总生存率为87.8%（95%置信区间：76.1 - 94.1）。综合征反应者的生存期优于无反应者，2年总生存率分别为93.9%（95%置信区间：92.2 - 98.0）和40.0%（95%置信区间：6.6 - 73.4）。共记录了233例不良事件。1 - 2级血液学毒性最为常见。
177 Lu-DOTATATE改善了F-NETs患者的症状和疾病控制。治疗耐受性良好。综合征对生活质量和总生存期均有影响。
