Abstract
Response to neoadjuvant immune checkpoint inhibitor (ICI)-based therapy in oncogene-driven resectable non-small cell lung cancer (NSCLC).
Author
person
Samuel Rosner
Johns Hopkins University, Baltimore, MD
info_outline
Samuel Rosner, Lavanya Sivapalan, Marianna Zahurak, Rohit Thummalapalli, Roni Rayes, Sydney Connor, Khaled Sanber, Joshua E. Reuss, Gavin Pereira, Kellie Nicole Smith, Valsamo Anagnostou, Stephen Broderick, David Randolph Jones, Julie R. Brahmer, Kristen A. Marrone, Jonathan Spicer, Jamie E. Chaft, Patrick M. Forde
Full text
Authors
person
Samuel Rosner
Johns Hopkins University, Baltimore, MD
info_outline
Samuel Rosner, Lavanya Sivapalan, Marianna Zahurak, Rohit Thummalapalli, Roni Rayes, Sydney Connor, Khaled Sanber, Joshua E. Reuss, Gavin Pereira, Kellie Nicole Smith, Valsamo Anagnostou, Stephen Broderick, David Randolph Jones, Julie R. Brahmer, Kristen A. Marrone, Jonathan Spicer, Jamie E. Chaft, Patrick M. Forde
Organizations
Johns Hopkins University, Baltimore, MD, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, Memorial Sloan Kettering Cancer Center, New York, NY, RI-MUHC, Montreal, QC, Canada, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, Johns Hopkins University School of Medicine, Baltimore, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, Johns Hopkins Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, Johns Hopkins Hospital, Baltimore, MD, McGill University Health Center, Montreal, QC, Canada
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
BMS, Stand Up 2 Cancer (SU2C)
Background:
Neoadjuvant (NEO) chemotherapy (chemo) plus nivolumab (nivo) has received FDA approval for treatment of resectable NSCLC, demonstrating superior event-free survival compared to chemo alone. However, outcomes of NEO ICI-based therapies in patients (pts) with oncogene-driven (OD)-NSCLC remains an unanswered question.
Methods:
We conducted a retrospective secondary analysis of pts enrolled in the clinical trial NCT02259621 with clinical stage I-IIIA NSCLC, treated with NEO ICI-based therapies: nivo alone, nivo+ipilimumab (ipi), or nivo+chemo followed by surgery. Pts underwent baseline genomic profiling using NGS. Pts with
KRAS
,
EGFR
,
MET
,
BRAF
,
ALK
,
HER2
,
ROS1
,
RET
or
NTRK
alterations were identified as OD-NSCLC.
STK11
and
KEAP1
mutations (muts) were also recorded. For pts who underwent definitive resection (DR) and baseline NGS testing, association of OD-status and clinical outcomes, including major pathologic response (MPR) and recurrence-free survival (RFS) are reported. Proportions are reported with exact 95% binomial confidence intervals (CI). Binomial probabilities are compared with Chi-square or Fisher’s exact tests. RFS and median follow-up (f/u) are reported using the Kaplan-Meier (KM) and reverse KM methods, respectively.
Results:
61 pts received NEO ICI-based therapy: 60% treated with nivo alone, 15% with ipi+nvo and 25% with chemo+nivo. 92% of pts underwent DR. Pathologic complete response (pCR) and MPR rates were, 12.5% and 37.5%, respectively. Baseline NGS testing was available for 47 pts, of whom, 49% had OD-NSCLC, with the majority (78%) harboring a
KRAS
mut. Additional OD alterations included non-classical
EGFR
(9%),
METex14
skipping (9%) and
ROS1
fusion (4%), of whom, 3/5 pts had a MPR after NEO-ICI.
STK11
muts were noted in 16% pts, and co-altered with
KRAS
in 9%. Median f/u for OD-NSCLC was 42.58 months. Pts with OD-NSCLC had comparable RFS after NEO-ICI compared to those with non-OD-NSCLC (HR 0.64, CI 0.19-2.13, p=0.5), including those with
KRAS
+ disease (HR 0.73, CI 0.2-2.73, p=0.6). Pts with co-mut
KRAS
+
STK11
+ trended toward shorter RFS compared to
KRAS
+
STK11
- (HR 6.36, CI 0.56-72.82, p=0.1).
STK11
+ also trended toward shorter RFS without reaching statistical significance (HR 2.51, CI 0.67-9.35, p=0.17). No significant associations between OD-status and MPR rates were seen, however
KRAS
+ (4/18) vs.
Kras
- (13/29) trended toward lower MPR rate (p=0.1). Four of 5 pts with disease progression preventing DR harbored an
STK11
or
KEAP1
mut.
Conclusions:
Findings from this cohort treated with various NEO ICI-based therapies, suggests comparable RFS, regardless of OD status- with the majority harboring
KRAS
muts. Lower MPR rates were observed for pts with
KRAS
+ tumors.
STK11
mut and
KRAS
+
STK11
+ co-mut status both trended toward shorter RFS, though definitive conclusions are limited by cohort size and treatment heterogeneity.
Clinical status
Clinical
1 clinical trial
12 organizations
3 drugs
13 targets
Clinical trial
Neoadjuvant Nivolumab, or Nivolumab in Combination With Ipilimumab, in Resectable Non-Small-Cell Lung Cancer.Status: Active (not recruiting), Estimated PCD: 2022-10-14
Organization
Memorial Sloan Kettering Cancer CenterOrganization
RI-MUHCOrganization
Johns Hopkins University School of MedicineOrganization
Johns Hopkins MedicineOrganization
Johns Hopkins HospitalOrganization
McGill University Health CenterDrug
nivolumabDrug
ipilimumabDrug
CisplatinTarget
CTLA-4Target
PD-1Target
ROS1Target
KRAS G12CTarget
BRAFTarget
ALKTarget
RETTarget
NTRKTarget
HER2 (ERBB2)Target
metastatic breast cancerTarget
KEAP1Target
STK11