Roeper Julia, Falk Markus, Chalaris-Rißmann Athena, Lueers Anne C, Ramdani Hayat, Wedeken Katrin, Stropiep Ursula, Diehl Linda, Tiemann Markus, Heukamp Lukas C, Otto-Sobotka Fabian, Griesinger Frank
Department of Internal Medicine-Oncology, Carl v. Ossietzky University of Oldenburg, Oldenburg, Germany.
Department of Hematology and Oncology, Pius-Hospital, Oldenburg, Germany.
Oncotarget. 2020 Jan 21;11(3):250-264. doi: 10.18632/oncotarget.27430.
The impact of TP53 co-mutations in EGFR mutated patients on PFS and OS is controversial. Different classifications of TP53 mutations with respect to functional and potential clinical impact have been published. Therefore, we retrospectively analyzed the impact of TP53 co-mutations on ORR, PFS and OS in a cohort of EGFR mutated NSCLC IV patients (UICC 7) using different classifications of TP53 mutations.
75 EGFR mutated NSCLC IV patients homogeneously treated with 1st line EGFR TKI were analyzed for TP53 co-mutations. TP53 mutations were classified according to three different types of classifications. The endpoints ORR, PFS and OS were investigated.
TP53 co-mutations were found in 29/59 patients (49.2%). TP53 co-mutations were a statistically significant independent negative predictive factor for ORR, PFS and OS. TP53 co-mutations were associated with inferior mPFS and mOS: mPFS/mOS 12 vs. 18/24 vs. 42 months for non-disruptive/disruptive mutations vs. WT ( < 0.004)/( < 0.009), 11 vs. 17/23 vs. 42 months for pathogenic vs. non-pathogenic/WT ( < 0.001)/( < 0.001), and 7 vs. 12 vs. 18/12 vs. 28 vs. 42 months for exon 8 vs. non-exon 8 vs. WT ( < 0.001)/( < 0.002).
TP53 co-mutations are frequent in EGFR mt+ NSCLC and have a strong negative impact on all clinical endpoints of TKI therapy.
EGFR突变患者中TP53共突变对无进展生存期（PFS）和总生存期（OS）的影响存在争议。关于TP53突变在功能和潜在临床影响方面的不同分类已被发表。因此，我们回顾性分析了TP53共突变对一组EGFR突变的非小细胞肺癌IV期患者（国际抗癌联盟第7版分期）的客观缓解率（ORR）、PFS和OS的影响，采用了不同的TP53突变分类方法。
对75例接受一线EGFR酪氨酸激酶抑制剂（TKI）同质治疗的EGFR突变的非小细胞肺癌IV期患者进行TP53共突变分析。TP53突变根据三种不同的分类类型进行分类。研究了ORR、PFS和OS等终点指标。
在29/59例患者（49.2%）中发现了TP53共突变。TP53共突变是ORR、PFS和OS的统计学显著独立负性预测因素。TP53共突变与较差的中位PFS和中位OS相关：非破坏性/破坏性突变与野生型相比，中位PFS/中位OS为12个月对18/24个月对42个月（<0.004）/（<0.009）；致病性与非致病性/野生型相比，为11个月对17/23个月对42个月（<0.001）/（<0.001）；外显子8与非外显子8与野生型相比，为7个月对12个月对18/12个月对28个月对42个月（<0.001）/（<0.002）。
TP53共突变在EGFR突变阳性的非小细胞肺癌中很常见，并且对TKI治疗的所有临床终点都有强烈的负面影响。
