Neoadjuvant nivolumab in early-stage non–small cell lung cancer (NSCLC): Five-year outcomes.

Authors

null

Samuel Rosner

Johns Hopkins University, Baltimore, MD

Samuel Rosner , Joshua E. Reuss , Marianna Zahurak , Janis M. Taube , Stephen Broderick , David Randolph Jones , Jamie E. Chaft , Patrick M. Forde

Organizations

Johns Hopkins University, Baltimore, MD, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, Johns Hopkins Departments of Dermatology, Pathology, Oncology and Bloomberg/Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, Memorial Sloan Kettering Cancer Center, New York, NY

Research Funding

Other Foundation

Background: Neoadjuvant (neoadj) immune checkpoint blockade (ICB) with anti-PD-1 therapy has shown increasing promise for early stage NSCLC, with long-term clinical outcomes still maturing. Our group reported the first phase I/II trial of neoadj nivolumab (nivo) in resectable NSCLC, finding therapy to be safe and feasible. We now present final clinical results from this cohort, representing the longest follow up data for neoadj anti-PD-1 to date. Methods: Two doses of neoadj nivo (3 mg/kg) were given prior to resection in 21 patients (pts) with resectable NSCLC. 5-year (yr) follow-up data, including recurrence-free survival (RFS), overall survival (OS) and association with pathologic response were tabulated. Event time distributions were estimated with the Kaplan-Meier method. All p-values are two-sided with 0.05 significance level. Results: At a median follow up of 63 months, 3-, 4- and 5-yr survival rates were 85, 80, and 80% respectively. RFS rates at 3-, 4- and 5-yrs were 65, 60, and 60% respectively. As previously reported, major pathologic response (MPR: ≤10% viable tumor) was 45%, and pathologic complete response (pCR) rate was 10%. The hazard ratio (HR) for pathologic down-staging was in the direction of improved RFS, without meeting statistical significance (HR 0.36, 95% CI 0.07-1.75, p = 0.2). RFS HR estimates for MPR and an alternative pathologic cut-off of less than 50% residual tumor (RT), were 0.61, (95% CI 0.15-2.44, p = 0.48) and 0.36, (95% CI 0.09-1.51, p = 0.16) respectively. The direction of the effect of pre-treatment PD-L1 positivity (≥1%) was to improve RFS (HR 0.36, 95% CI 0.07-1.85, p = 0.22). At 5-yr follow up, 8 of 9 (89%) pts with MPR were alive and no cancer deaths have occurred. Amongst pts with MPR, 1/9 pts had a cancer recurrence in the mediastinum treated successfully with definitive chemoradiotherapy. Both pts with pCR are alive and without recurrence. Patterns of all recurrences in this cohort are summarized in table 1. No long-term immune-related adverse events have occurred other than one G3 dermatologic event. Conclusions: The 5-yr clinical outcomes for neoadj nivo in resectable NSCLC compare favorably to historical trends. MPR trended toward improved RFS, while definitive conclusions are limited by our cohort size and overall low recurrence rate. Thresholds of %RT beyond pCR and MPR in this setting should be explored in larger prospective studies. PD-L1 expression may play a role in predicting long-term response, but larger prospective studies are needed. Clinical trial information: NCT02259621.

Pre-treatment stage
Histology
PD-L1 (%)
Notable Mutations
%RT
Adjuvant chemotherapy (Y/N)
RFS duration (months)
Local vs. Distant Recurrence (L/D)
Alive (Y/N)
IIIA
Squam
0
TP53
80
N
10.4
D
N
IIA
Adeno
0
Kras G12c, STK11
75
Y
1.8
D
Y
IIIA
Adeno
N/A
-
5
N
8.5
L
Y
IIIA
Squam
25
-
30
N
20.3
D
N
IIIA
Adeno
60
Ros1
95
N
23.1
D
Y
IIB
Adeno
0
F11R-NRG1 fusion
100
N
29.3
L
N
IA
Adeno
0
-
100
N
46.5
L
Y

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Track

Lung Cancer

Sub Track

Local-Regional Non–Small Cell Lung Cancer

Clinical Trial Registration Number

NCT02259621

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 8537)

DOI

10.1200/JCO.2022.40.16_suppl.8537

Abstract #

8537

Poster Bd #

164

Abstract Disclosures