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. 2019 Aug 1;30(8):1321-1328.
doi: 10.1093/annonc/mdz167.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

J Mazieres  1 , A Drilon  2 , A Lusque  3 , L Mhanna  4 , A B Cortot  5 , L Mezquita  6 , A A Thai  7 , C Mascaux  8 , S Couraud  9 , R Veillon  10 , M Van den Heuvel  11 , J Neal  12 , N Peled  13 , M Früh  14 , T L Ng  15 , V Gounant  16 , S Popat  17 , J Diebold  18 , J Sabari  2 , V W Zhu  19 , S I Rothschild  20 , P Bironzo  21 , A Martinez-Marti  22 , A Curioni-Fontecedro  23 , R Rosell  24 , M Lattuca-Truc  25 , M Wiesweg  26 , B Besse  6 , B Solomon  7 , F Barlesi  8 , R D Schouten  11 , H Wakelee  12 , D R Camidge  15 , G Zalcman  16 , S Novello  21 , S I Ou  19 , J Milia  4 , O Gautschi  27
Affiliations

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

J Mazieres et al. Ann Oncol. .

Abstract

Background: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.

Patients and methods: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.

Results: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).

Conclusions: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Keywords: immunotherapy; lung cancer; oncogenic addiction.

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Figures

Supplementary Data
Supplementary Data
Figure 1
Figure 1
Best response to ICI according to RECIST criteria (PD, progressive disease; SD, stable disease; PR, partial response; CR, complete response).
Figure 2
Figure 2
Overall survival (on the left) and progression-free survival (on the right) in the whole cohort (upper figures) and in each subgroup (lower figures).
Figure 3
Figure 3
PFS according to oncogenic drivers’ variants and PDL1 expression.
See this image and copyright information in PMC

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