Riudavets Mariona, Auclin Edouard, Mosteiro Miguel, Dempsey Naomi, Majem Margarita, Lobefaro Riccardo, López-Castro Rafael, Bosch-Barrera Joaquim, Pilotto Sara, Escalera Elena, Tagliamento Marco, Mosquera Joaquin, Zalcman Gerard, Aboubakar-Nana Frank, Ponce Santiago, Dal Maso Alessandro, Spotti Martina, Mielgo-Rubio Xabier, Mussat Elodie, Reyes Roxana, Benítez José-Carlos, Lupinacci Lorena, Duchemann Boris, De Giglio Andrea, Blaquier Juan, Audigier-Valette Clarisse, Scheffler Matthias, Nadal Ernest, Lopes Gilberto, Signorelli Diego, Garcia-Campelo Rosario, Menis Jessica, Bluthgen Virginia, Campayo Marc, Recondo Gonzalo, Besse Benjamin, Planchard David, Mezquita Laura
Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France.
Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP Centre, Université de Paris, Paris, France.
Eur J Cancer. 2022 May;167:142-148. doi: 10.1016/j.ejca.2022.02.014. Epub 2022 Mar 17.
Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised.
Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA.
Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02).
We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings.
度伐利尤单抗是不可切除的 III 期非小细胞肺癌（NSCLC）放化疗后巩固治疗的标准疗法；然而，其在携带驱动基因改变（dGA）的 NSCLC 患者中的活性特征尚不明确。
多中心回顾性研究，纳入 2015 年 4 月至 2020 年 10 月期间在欧美 26 个中心接受放化疗后使用度伐利尤单抗治疗的不可切除 III 期 NSCLC 患者。收集临床和生物学数据；dGA 包括：表皮生长因子受体（EGFR）/ 原癌基因 B-Raf（BRAF）/ Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变（m）和间变性淋巴瘤激酶（ALK）/ 原癌基因酪氨酸蛋白激酶受体（ROS1）重排（r）。我们基于 dGA 评估无进展生存期（PFS）和总生存期（OS）。
在纳入的 323 例患者中，43 例患者存在一种 dGA：KRAS 突变（n = 26；8 例 G12C）、EGFR 突变（n = 8；6 例 del19/ex21）、BRAF 突变（n = 5；4 例 V600E）和 ALK 重排（n = 4）。中位年龄为 66 岁[39 - 84]，性别比为 1:1，98%的患者体能状态（PS）为 0 - 1，19%为非吸烟者；88%为腺癌。程序性死亡受体配体 1（PD-L1）阳性率为 85%（n = 4 例缺失）。在整个队列中，中位 PFS 为 17.5 个月（mo.）（95%置信区间[CI]，13.2 - 24.9），中位 OS 为 47 个月（95%CI，47 - 未达到[NR]）。dGA 患者与非 dGA 患者之间未观察到中位 PFS 有统计学显著差异：14.9 个月（95%CI，8.1 - NR）对 18 个月（95%CI，13.4 - 28.3）（P = 1.0）；然而，单独分析时：KRAS 突变 G12C 患者的中位 PFS 未达到（11.3 - NR），EGFR 突变 del19/ex21 患者为 8.1 个月（5.8 - NR），BRAF 突变 V600E/ALK 重排患者为 7.8 个月（7.7 - NR）（P = 0.02）。
我们观察到度伐利尤单抗巩固治疗在伴有 EGFR/BRAF 突变和 ALK 重排的不可切除 III 期 NSCLC 患者中的活性有限，但对携带 KRAS 突变的患者无效。需要更大规模的前瞻性研究来证实这些发现。
