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 th...
