Journal of Clinical Oncology

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ISSN / EISSN : 0732-183X / 1527-7755
Total articles ≅ 80,395
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, Aimee Jackson, Justin Loke, Shamyla Siddique, Andrea Hodgkinson, John Mason, Georgia Andrew, Sandeep Nagra, Ram Malladi, Andrew Peniket, et al.
Journal of Clinical Oncology, Volume 39, pp 768-778; doi:10.1200/jco.20.02308

PURPOSE Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials. PATIENTS AND METHODS Two hundred forty-four patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) were randomly assigned 1:1 to a fludarabine-based RIC regimen or FLAMSA-Bu. Pretransplant measurable residual disease (MRD) was monitored by flow cytometry (MFC-MRD) and correlated with outcome. RESULTS There was no difference in 2-year overall survival (hazard ratio 1.05 [85% CI, 0.80 to 1.38] P = .81) or cumulative incidence of relapse (CIR) (hazard ratio 0.94 [95%CI, 0.60 to 1.46] P = .81) between the control and FLAMSA-Bu arms. Detectable pretransplant MFC-MRD was associated with an increased CIR (2-year CIR 41.0% v 20.0%, P = .01) in the overall trial cohort with a comparable prognostic impact when measured by an unsupervised analysis approach. There was no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Acquisition of full donor T-cell chimerism at 3 months abrogated the adverse impact of pretransplant MRD on CIR and overall survival. CONCLUSION The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML.
Amar Gajjar, , Kyle S. Smith, Tong Lin, , Murali Chintagumpala, Anita Mahajan, Jack Su, , Ute Bartels, et al.
Journal of Clinical Oncology, Volume 39, pp 822-835; doi:10.1200/jco.20.01372

The publisher has not yet granted permission to display this abstract.
, , Eleanor Hudson, Jenny Hewison, Carolyn Morris, Patricia Holch, Robert Carter, Andrea Gibson, Marie Holmes, Beverly Clayton, et al.
Journal of Clinical Oncology, Volume 39, pp 734-747; doi:10.1200/jco.20.02015

The publisher has not yet granted permission to display this abstract.
Vinod Sharma, Akash Kumar
Journal of Clinical Oncology, Volume 39, pp 861-862; doi:10.1200/jco.20.02772

Masaki Uchihara, Kenichi Yoshimura, , Yukino Kawamura, Chikako Shimizu
Journal of Clinical Oncology, Volume 39, pp 862-863; doi:10.1200/jco.20.02907

, , Philip L. McCarthy
Journal of Clinical Oncology, Volume 39, pp 836-839; doi:10.1200/jco.20.03326

, Scott Gettinger, , Laura Q. M. Chow, Marco Angelo Burgio, , Adam Pluzanski, , Osvaldo Arén Frontera, Rita Chiari, et al.
Journal of Clinical Oncology, Volume 39, pp 723-733; doi:10.1200/jco.20.01605

PURPOSE Immunotherapy has revolutionized the treatment of advanced non–small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3–5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.
Feng-Hua Wang, Xiao-Li Wei, Jifeng Feng, Qi Li, Nong Xu, Xi-Chun Hu, Wangjun Liao, Yi Jiang, Xiao-Yan Lin, Qing-Yuan Zhang, et al.
Journal of Clinical Oncology, Volume 39, pp 704-712; doi:10.1200/jco.20.02712

PURPOSE As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1− patients, respectively ( P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% ( P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.
Michael J. Raphael, , Xuejiao Wei, , , , D. Robert Siemens, Andrew G. Robinson, Christopher M. Booth
Journal of Clinical Oncology, Volume 39, pp 779-786; doi:10.1200/jco.20.02298

The publisher has not yet granted permission to display this abstract.
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