Department of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Perthera, McLean, VA, USA.
Perthera, McLean, VA, USA.
Lancet Oncol. 2020 Apr;21(4):508-518. doi: 10.1016/S1470-2045(20)30074-7. Epub 2020 Mar 2.
About 25% of pancreatic cancers harbour actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) programme includes US patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. We sought to determine whether patients with pancreatic cancer whose tumours harboured such actionable molecular alterations and who received molecularly matched therapy had a longer median overall survival than similar patients who did not receive molecularly matched therapy.
In this retrospective analysis, treatment history and longitudinal survival outcomes were analysed in patients aged 18 years or older with biopsy-confirmed pancreatic cancer of any stage, enrolled in the KYT programme and who received molecular testing results. Since the timing of KYT enrolment varied for each patient, the primary outcome measurement of median overall survival was calculated from the initial diagnosis of advanced disease until death. We compared median overall survival in patients with actionable mutations who were treated with a matched therapy versus those who were not treated with a matched therapy.
Of 1856 patients with pancreatic cancer who were referred to the KYT programme between June 16, 2014, and March 31, 2019, 1082 (58%) patients received personalised reports based on their molecular testing results. Actionable molecular alterations were identified in 282 (26%) of 1082 samples. Among 677 patients for whom outcomes were available, 189 had actionable molecular alterations. With a median follow-up of 383 days (IQR 214-588), those patients with actionable molecular alterations who received a matched therapy (n=46) had significantly longer median overall survival than did those patients who only received unmatched therapies (n=143; 2·58 years [95% CI 2·39 to not reached] vs 1·51 years [1·33-1·87]; hazard ratio 0·42 [95% CI 0·26-0·68], p=0·0004). The 46 patients who received a matched therapy also had significantly longer overall survival than the 488 patients who did not have an actionable molecular alteration (2·58 years [95% CI 2·39 to not reached] vs 1·32 years [1·25-1·47]; HR 0·34 [95% CI 0·22-0·53], p<0·0001). However, median overall survival did not differ between the patients who received unmatched therapy and those without an actionable molecular alteration (HR 0·82 [95% CI 0·64-1·04], p=0·10).
These real-world outcomes suggest that the adoption of precision medicine can have a substantial effect on survival in patients with pancreatic cancer, and that molecularly guided treatments targeting oncogenic drivers and the DNA damage response and repair pathway warrant further prospective evaluation.
Pancreatic Cancer Action Network and Perthera.
约 25%的胰腺癌存在可采取的分子改变，这些改变是指具有临床或强烈临床前证据表明某种特定疗法具有预测获益的分子改变。“了解您的肿瘤”（KYT）计划纳入了美国的胰腺癌患者，并使患者能够接受商业上可用的多组学分析，从而提供针对性的治疗选择和临床试验建议。我们旨在确定是否存在这些可采取的分子改变且接受了分子匹配治疗的胰腺癌患者的中位总生存期长于未接受分子匹配治疗的类似患者。
在这项回顾性分析中，分析了年龄在 18 岁或以上、经活检证实患有任何阶段胰腺癌的患者的治疗史和纵向生存结局，这些患者在 KYT 计划中接受了分子检测。由于每位患者的 KYT 入组时间不同，因此将初始诊断为晚期疾病至死亡的中位总生存期作为主要结局测量。我们比较了存在可采取的突变且接受了匹配治疗的患者与未接受匹配治疗的患者的中位总生存期。
在 2014 年 6 月 16 日至 2019 年 3 月 31 日期间被转介至 KYT 计划的 1856 例胰腺癌患者中，1082 例（58%）患者接受了基于其分子检测结果的个性化报告。在 1082 个样本中，282 个（26%）确定了可采取的分子改变。在可获得结局的 677 例患者中，189 例存在可采取的分子改变。中位随访 383 天（IQR：214-588），接受了匹配治疗的 189 例存在可采取的分子改变的患者的中位总生存期明显长于仅接受了不匹配治疗的患者（46 例 vs 143 例；2.58 年[95%CI：2.39 至未达到] vs 1.51 年[1.33-1.87]；风险比 0.42[95%CI：0.26-0.68]，p=0.0004）。接受了匹配治疗的 46 例患者的总生存期也明显长于 488 例未发生可采取的分子改变的患者（2.58 年[95%CI：2.39 至未达到] vs 1.32 年[1.25-1.47]；HR 0.34[95%CI：0.22-0.53]，p<0.0001）。然而，接受不匹配治疗的患者与不存在可采取的分子改变的患者的中位总生存期无差异（HR 0.82[95%CI：0.64-1.04]，p=0.10）。
这些真实世界的结局表明，采用精准医学可以对胰腺癌患者的生存产生重大影响，靶向致癌驱动基因和 DNA 损伤反应及修复途径的分子指导治疗值得进一步前瞻性评估。
胰腺癌行动网络和 Perthera。
