Zie ook dit artikel:

https://kanker-actueel.nl/aanbevolen-abstracten-van-asco-2019-over-longkanker-en-van-commentaar-voorzien-door-artsen-werkzaam-bij-asco-zelf.html

12 juni 2019: Bron: N Engl J Med. 2017 Jun 22; 376(25): 2415–2426.

Klik op de titel van de studie voor het volledige studierapport. Daaronder abstract plus referentielijst. Zie verder in gerelateerde artikelen.

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

Geselecteerde subgroepen
Over de meeste geplande subgroepen (inclusief alle patiënten die randomisatie hadden ondergaan), waren de resultaten van de analyses van progressievrije overleving en algehele overleving consistent met de algehele onderzoeksresultaten (Fig. 2A and and2B).2B).

De enige vooraf gespecificeerde subgroep waren patiënten gedefinieerd volgens histologische bevindingen (een stratificatiefactor); patiënten met histologische resultaten die plaveiselcel NSCLC vertoonden hadden een iets langere progressievrije overleving en totale overleving met nivolumab dan met chemotherapie, hoewel de resultaten niet significant waren (Fig. 2A and and2B2B).

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Figure 2 (facing page).

Exploratory Subgroup Analyses of Progression-free Survival and Overall Survival.

Panel A shows the subgroup analysis of progression-free survival involving all the patients who underwent random ization, and Panel B the subgroup analysis of overall survival. PD-L1 denotes programmed death ligand 1. The Eastern Cooperative Oncology Group (ECOG) per formance-status score is assessed on a 5-point scale, with higher numbers indicating greater disability. Panel C shows the analysis of progression-free survival among patients who could be evaluated for tumor-mutation burden and who had a high burden. NR denotes not reached. Panel D shows the analysis of progression-free survival among patients who could be evaluated for tumor-mutation burden and who had a low or medium burden. The data for patients with a low or medium tumor-mutation burden were pooled.

En hier het abstract van de studie:

2017 Jun 22;376(25):2415-2426. doi: 10.1056/NEJMoa1613493.

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Carbone DP¹, Reck M¹, Paz-Ares L¹, Creelan B¹, Horn L¹, Steins M¹, Felip E¹, van den Heuvel MM¹, Ciuleanu TE¹, Badin F¹, Ready N¹, Hiltermann TJN¹, Nair S¹, Juergens R¹, Peters S¹, Minenza E¹, Wrangle JM¹, Rodriguez-Abreu D¹, Borghaei H¹, Blumenschein GR Jr¹, Villaruz LC¹, Havel L¹, Krejci J¹, Corral Jaime J¹, Chang H¹, Geese WJ¹, Bhagavatheeswaran P¹, Chen AC¹, Socinski MA¹; CheckMate 026 Investigators.

Collaborators (140)

Lupinacci L, Martin C, Pilnik N, Richardet ME, Varela MS, Adams J, Boyer M, John T, Moore M, O'Byrne K, Eckmayr J, Pirker R, Decoster L, van Meerbeeck J, Vansteenkiste J, Surmont V, Barrios CH, Franke FA, Pinto G, Blais N, Foley MC, Juergens R, Leighl N, Morris DG, Havel L, Kolek V, Krejci J, Reiterer P, Roubec J, Ahvonen J, Jekunen A, Maasilta P, Barlesi F, Dansen E, Fraboulet G, Lena H, Mennecier B, Zalcman G, Frickhofen N, Kohlhaeufl M, Reck M, Repp R, Steins M, Wolf J, Agelaki S, Syrigos K, Albert I, Ostoros G, Szilasi M, Cappuzzo F, Crino L, De Marinis F, Gridelli C, Morabito A, Roila F, Atagi S, Fujita S, Hida T, Hirashima T, Maemondo M, Minato K, Nakagawa K, Nishio M, Nogami N, Ohe Y, Saka H, Sakai H, Satouchi M, Takeda K, Tanaka H, Yamamoto N, Arrieta-Rodriguez O, De la Mora Jimenez E, Flores Wilbert V, Aerts J, Hiltermann TJN, Van Den Heuvel M, Chmielowska E, Czyzewicz G, Gabrys J, Kalinka-Warzocha E, Pluzanski A, Kim HR, Kim SW, Park K, Cainap C, Ciuleanu TE, Ghizdavescu D, Blasco A, Corral Jaime J, De Castro J, Felip E, Paz-Ares L, Rodriguez Abreu D, Trigo J, Kölbeck KG, Lindskog M, Curioni-Fontecedro A, Mark M, Peters S, Chen YM, Karaca H, Chao D, Mulatero C, Summers Y, Arledge S, Badin F, Batus M, Blumenschein G, Borghaei H, Camidge R, Boyd T, Brahmer J, Carbone D, Cetnar J, Chachoua A, Chaft J, Chen H, Creelan B, Gainor J, Gettinger S, Gerber DE, Horn L, Kaywin P, Kessler R, Langer CJ, McCracken J, Nair S, Oyola R, Pillai R, Quddus F, Rangachari D, Ready N, Reynolds C, Rosenberg R, Sharma N, Stinchcombe T, Villaruz L, Wakelee H, Wrangle J.

Author information

1: From the Ohio State University Comprehensive Cancer Center, Columbus (D.P.C.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.), and Thoraxklinik, Heidelberg University Hospital, Heidelberg (M.S.) - both in Germany; Hospital Universitario Doce de Octubre, Centro Nacional de Investigaciones Oncológicas and Universidad Complutense, Madrid (L.P.-A., J.C.J.), Vall d'Hebron University Hospital, Barcelona (E.F.), and Hospital Universitario Insular de Gran Canaria, Las Palmas (D.R.-A.) - all in Spain; H. Lee Moffitt Cancer Center, Tampa, FL (B.C.); Vanderbilt University Medical Center, Nashville (L. Horn); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (M.M.H.), and University of Groningen, Universitair Medisch Centrum Groningen, Groningen (T.J.N.H.) - both in the Netherlands; Prof. Dr. Ion Chiricuta Institute of Oncology and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Baptist Health Lexington, Lexington, KY (F.B.); Duke University, Durham, NC (N.R.); Lehigh Valley Health Network, Allentown (S.N.), Fox Chase Cancer Center, Philadelphia (H.B.), and University of Pittsburgh Medical Center Cancer Center, Pittsburgh (L.C.V., M.A.S.) - all in Pennsylvania; Juravinski Cancer Centre, Hamilton, ON, Canada (R.J.); Oncology Department, Lausanne University Hospital, Lausanne, Switzerland (S.P.); Santa Maria Hospital, Terni, Italy (E.M.); Hollings Cancer Center, Charleston, SC (J.M.W.); Department of Thoracic-Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.R.B.); Klinika Pneumologie a Hrudní Chirurgie, Nemocnice Na Bulovce, Prague, Czech Republic (L. Havel, J.K.); and Bristol-Myers Squibb, Princeton, NJ (H.C., W.J.G., P.B., A.C.C.).

Abstract

BACKGROUND:

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC.

METHODS:

We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more.

RESULTS:

Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval , 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy.

CONCLUSIONS:

Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .).

Comment in

Nivolumab as first-line treatment in non-small cell lung cancer patients-key factors: tumor mutation burden and PD-L1 ≥50. [Transl Lung Cancer Res. 2018]
Companion and complementary diagnostics for first-line immune checkpoint inhibitor treatment in non-small cell lung cancer. [Transl Lung Cancer Res. 2018]
Lung Cancer: Frontline nivolumab - CheckMate 026 ends in stalemate. [Nat Rev Clin Oncol. 2017]

Comment on

Cancer Immunotherapy Trials Not Immune from Imprecise Selection of Patients. [N Engl J Med. 2017]

PMID:: 28636851
PMCID:: PMC6487310
DOI:: 10.1056/NEJMoa1613493

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