Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study.

Cascone, Tina; William, William Nassib; Weissferdt, Annikka; Lin, Heather; Leung, Cheuk Hong; Carter, Brett W.; Fossella, Frank V.; Mott, Frank E.; Papadimitrakopoulou, Vassiliki A.; Blumenschein, George R.; Le, Xiuning; Cuentas, Edwin Roger Parra; Bernatchez, Chantale; Wistuba, Ignacio I.; Vaporciyan, Ara A.; Gibbons, Don L.; Swisher, Stephen G.; Heymach, John V.; Sepesi, Boris

doi:10.1200/jco.2019.37.15_suppl.8504

Cited by 124 publications

(165 citation statements)

References 0 publications

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…Grade 3 or higher TRAEs were observed in 33% of enrolled patients in our study, a numerically higher rate than that reported in an interim presentation of the NEOSTAR study, an ongoing phase II single-center study which randomized 44 patients with resectable NSCLC to neoadjuvant nivolumab or nivolumab plus ipilimumab. 11 Differences in toxicity rates are likely attributable to sample size and overall the observed rate of ≥G3 TRAEs in our study was similar to that seen with nivolumab plus ipilimumab in advanced NSCLC 6 and in neoadjuvant studies of resectable melanoma. 12 Nevertheless, the toxicity in our study arm exceeded that reported in neoadjuvant studies of anti-PD1 monotherapy 4 11 13 14 and combination ICB plus chemotherapy, 15 16 which was a major determinant in our decision to terminate this study arm early.…”

Section: Discussionsupporting

confidence: 70%

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer

Reuss

Anagnostou

Cottrell

et al. 2020

J Immunother Cancer

121

101

View full text Add to dashboard Cite

BackgroundWe conducted the first trial of neoadjuvant PD-1 blockade in resectable non-small cell lung cancer (NSCLC), finding nivolumab monotherapy to be safe and feasible with an encouraging rate of pathologic response. Building on these results, and promising data for nivolumab plus ipilimumab (anti-CTLA-4) in advanced NSCLC, we expanded our study to include an arm investigating neoadjuvant nivolumab plus ipilimumab.MethodsPatients with resectable stage IB (≥4 cm)–IIIA (American Joint Committee on Cancer Tumor Node Metastases seventh edition), histologically confirmed, treatment-naïve NSCLC received nivolumab 3 mg/kg intravenously plus ipilimumab 1 mg/kg intravenously 6 weeks prior to planned resection. Nivolumab 3 mg/kg was given again approximately 4 and 2 weeks preoperatively. Primary endpoints were safety and feasibility with a planned enrollment of 15 patients. Pathologic response was a key secondary endpoint.ResultsWhile the treatment regimen was feasible per protocol, due to toxicity, the study arm was terminated early by investigator consensus after 9 of 15 patients were enrolled. All patients received every scheduled dose of therapy and were fit for planned surgery; however, 6 of 9 (67%) experienced treatment-related adverse events (TRAEs) and 3 (33%) experienced grade ≥3 TRAEs. Three of 9 patients (33%) had biopsy-confirmed tumor progression precluding definitive surgery. Of the 6 patients who underwent resection, 3 are alive and disease-free, 2 experienced recurrence and are actively receiving systemic treatment, and one died postoperatively due to acute respiratory distress syndrome. Two patients who underwent resection had tumor pathologic complete responses (pCRs) and continue to remain disease-free over 24 months since surgery. Pathologic response correlated with pre-treatment tumor PD-L1 expression, but not tumor mutation burden. Tumor KRAS/STK11 co-mutations were identified in 5 of 9 patients (59%), of whom two with disease progression precluding surgery had tumor KRAS/STK11/KEAP1 co-mutations.ConclusionsThough treatment was feasible, due to toxicity the study arm was terminated early by investigator consensus. In light of this, and while the long-term disease-free status of patients who achieved pCR is encouraging, further investigation of neoadjuvant nivolumab plus ipilimumab in patients with resectable NSCLC requires the identification of predictive biomarkers that enrich for response.

show abstract

Section: Discussionsupporting

confidence: 70%

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer

Reuss

Anagnostou

Cottrell

et al. 2020

J Immunother Cancer

121

101

View full text Add to dashboard Cite

show abstract

“…Compared with the Checkmate-159 study, 17 a similar MPR rate (40.5% versus 45%) and superior ORR (20.0% versus 10%) were observed in our study. Regarding the NEOSTAR study, 26 a superior MPR (40.5% versus 17%), similar ORR (20.0% versus 22%), and pCR (8.1% versus 9%) was identified in current study compared with single nivolumab neoadjuvant treatment group. Moreover, the median degree of pathologic remission in primary tumor was 50% in our study.…”

Section: Discussionsupporting

confidence: 52%

“…Another G5 TRAE was pneumonia-caused death after operation that was also reported in single nivolumab treatment group of the NEOSTAR study. 26 Two patients postponed operation because of treatment-related grade 2 AE. Therefore, generally, neoadjuvant sintilimab was well tolerated.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC

Gao

et al. 2020

Journal of Thoracic Oncology

300

273

View full text Add to dashboard Cite

Introduction: Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting. Methods: Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomographycomputed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726). Results: A total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p ¼ 0.0471).

show abstract

“…29 In a recent presentation, the NEOSTAR phase 2 trial demonstrated higher rates of major pathological response in patients receiving combination nivolumab plus ipilimumab compared with those receiving nivolumab monotherapy before surgery. 30 Overall, both therapeutic regimens were well tolerated; however, surgical complications included 2 bronchopleural fistulas and 8 air leaks. 30 These early results are promising from a feasibility and safety standpoint.…”

Section: Current Literature and Ongoing Trialsmentioning

confidence: 91%

“…30 Overall, both therapeutic regimens were well tolerated; however, surgical complications included 2 bronchopleural fistulas and 8 air leaks. 30 These early results are promising from a feasibility and safety standpoint. They suggest limited surgical delays and adequate resection; however, the technical considerations in using these therapies preoperatively has generated little discussion to date.…”

Section: Current Literature and Ongoing Trialsmentioning

confidence: 91%

The immunotherapeutic landscape in non–small cell lung cancer and its surgical horizons

Rhodin

Rucker

Ready

et al. 2020

The Journal of Thoracic and Cardiovascular Surgery

View full text Add to dashboard Cite

Lung cancer continues to be a leading cause of cancer-related death worldwide. Despite tremendous advances in surgical technique, chemotherapy regimens, radiation, and targeted therapies, survival is <50% at 5 years. Immunotherapy, specifically immune checkpoint inhibitors (ICIs), demonstrates promise as a solution to this clinical problem. Several agents have been Food and Drug Administration-approved for locally advanced and metastatic non-small cell lung cancer (NSCLC). Further studies are now exploring the use of these agents in the neoadjuvant and adjuvant settings. Although ICIs have demonstrated meaningful efficacy in NSCLC and other advanced malignancies, they are not without adverse toxicities. Furthermore, there are minimal data on their use in the perioperative period. Here we discuss the current domain of ICIs and their surgical implications in NSCLC.

show abstract

Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study.

Cited by 124 publications

References 0 publications

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer

Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC

The immunotherapeutic landscape in non–small cell lung cancer and its surgical horizons

Contact Info

Product

Resources

About