2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Type: Oral Abstract Session
Time: Saturday June 1, 1:15 PM to 4:15 PM
Location: Hall D2
Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study.
Local-Regional Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 8504)
Author(s): Tina Cascone, William Nassib William, Annikka Weissferdt, Heather Y. Lin, Cheuk Hong Leung, Brett W. Carter, Frank V. Fossella, Frank Mott, Vassiliki Papadimitrakopoulou, George R. Blumenschein, Jr., Xiuning Le, Lorenzo Federico, Edwin Roger Parra Cuentas, Chantale Bernatchez, Ignacio Ivan Wistuba, Ara A. Vaporciyan, Don Lynn Gibbons, Stephen Swisher, John Heymach, Boris Sepesi, NEOSTAR Study Group; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Texas MD Anderson Cancer Center, Houston, TX; Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Background: Neoadjuvant immune checkpoint inhibitors (ICIs) induce major pathologic response (MPR) rates of 20 to 45% in resected NSCLCs. We report the results of NEOSTAR - a phase 2 trial of neoadjuvant N or NI for NSCLCs. Methods: Pts with stage I-IIIA (single N2) resectable NSCLC (AJCC 7th), PS 0-1, were randomized to N (3 mg/kg IV, D1, 15, 29) or N plus I (1 mg/kg IV, D1) followed by surgery (n = 44). Primary endpoint: MPR (≤10% viable tumor), hypothesized to be higher than MPR to induction chemotherapy historical controls. Tumor immune infiltrates and pre- & post-ICI tumor PD-L1 % were assessed by flow cytometry & IHC. Wilcoxon ranked sum test & Fisher’s exact test were used for comparisons. Results: 44 pts were randomized, 23 N, 21 NI: mean age 66, 64% males, 18% never smokers, 59% adenocarcinomas, stages: IA 8 (18%), IB 15 (34%), IIA 7 (16%) IIB 5 (11%); IIIA 9 (20%). Only 3 pts received < 3 doses due to TRAEs (7%). 34 pts had surgery post ICIs (7 not resected [7/41], 17%, [2 N, 5 NI], 3 pending). There were 10 MPRs in 41 pts overall (24%, 4 N, 6 NI), of which 6 were path CRs (15%, 2 N [9%], 4 NI [21%]). Among 34 resected pts, MPR rate was 29% (N 20%, NI 43%). Median % of viable tumor was lower post NI vs N (20% vs 65%, p = .097). ORR (RECIST v1.1) was 22% (8 PRs [5 N, 3 NI], 1 CR [NI]); 15% of pts had PD (3 N, 3 NI). The proportion of CR+PR in MPR+ was higher than in MPR- (6 [60%] vs 2 [7%], p < .001). Surgical complications included 2 bronchopleural fistulas (BPFs) in N & 8 air leaks (5 N, 3 NI). G3-G5 TRAEs included a death due to BPF post steroid-treated pneumonitis (G5, N); G3 pneumonia, hypoxia, hypermagnesemia (1 each, all N), G3 diarrhea (1 NI). CD3+& CD103+ tissue resident memory CD8+ TILs were higher in NI- vs N-treated tumors (CD3+ 81.2% vs 54.4%, p = .028; CD8+ 56.2% vs 38.3%, p = .069). Median pre-treatment tumor PD-L1 was higher in responders (MPR+, CR+PR) vs non-responders (80% vs 1%, p = .024), and the % of viable tumor was lower in tumors with PD-L1 > 1% vs PD-L1 ≤1% (median 20% vs 80%, p = .046). Conclusions: Overall a 24% MPR rate to neoadjuvant ICIs was observed. NI induced a higher % of non-viable tumor and of tissue resident memory TILs vs N. Antitumor activity was associated with higher pre-treatment PD-L1 levels. Clinical trial information: NCT03158129
Meeting: 2019 ASCO Annual Meeting Abstract No: 8502 First Author: Theodoros Tsakiridis
Meeting: 2019 ASCO Annual Meeting Abstract No: 8503 First Author: David J. Kwiatkowski
3. Neoadjuvant chemo-immunotherapy for the treatment of stage IIIA resectable non-small-cell lung cancer (NSCLC): A phase II multicenter exploratory study—Final data of patients who underwent surgical assessment.
Meeting: 2019 ASCO Annual Meeting Abstract No: 8509 First Author: Mariano Provencio