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Proffered Paper 2 – Non-metastatic NSCLC and other thoracic malignancies (mesothelioma and thymic carcinoma)

5378 - 2nd/3rd-line Nivolumab vs Nivo plus Ipilimumab in Malignant Pleural Mesothelioma: long-term results of IFCT-1501 MAPS2 phase 2R trial with a focus on hyperprogression (HPD)


30 Sep 2019


Proffered Paper 2 – Non-metastatic NSCLC and other thoracic malignancies (mesothelioma and thymic carcinoma)


Tumour Site



Gerard Zalcman


Annals of Oncology (2019) 30 (suppl_5): v747-v755. 10.1093/annonc/mdz266


G. Zalcman1, J. Mazieres2, L. Greillier3, S. Brosseau1, S. Lantuejoul4, P. DO5, O. Bylicki6, I. Monnet7, R. Corre8, C. Audigier-Valette9, M. Locatelli-Sanchez10, O. Molinier11, F. Guisier12, T. Urban13, D. Planchard14, C. Ligeza-Poisson15, E. Amour16, F. Morin17, D. Moro-Sibilot18, A. Scherpereel19

Author affiliations

  • 1 Thoracic Oncology, AP-HP Hopital Bichat Claude Bernard, 75018 - Paris/FR
  • 2 Thoracic Oncology, Hospital Larrey, CHU Toulouse, 31400 - Toulouse/FR
  • 3 Multidisciplinary Oncology And Therapeutic Innovations, Hopital Nord Assistance Publique Hopitaux de Marseille, 13009 - Marseille/FR
  • 4 Pathology, Mesopath Group, Centre Léon Bérard, 69008 - Lyon/FR
  • 5 Thoracic Oncology, Cancer Center François Baclesse, 14032 - CAEN/FR
  • 6 Pneumologie Et Oncologie Thoracique, Military Hospital HIA Percy, 92140 - Clamart/FR
  • 7 Pulmonology, CH Intercommunal de Créteil, 94010 - Créteil/FR
  • 8 Pulmonology, CHU de Pontchaillou, 35033 - Rennes/FR
  • 9 Pneumology, Hôpital Sainte Musse, 83000 - Toulon/FR
  • 10 Pulmonology And Thoracic Oncology, Hôpital Lyon-Sud, 69310 - Pierre-Benite/FR
  • 11 Pulmonology, Centre Hospitalier Du Mans, 72037 - Le Mans/FR
  • 12 Pulmonology, Hop. Charles Nicolle, 76000 - Rouen/FR
  • 13 Pulmonology, CHU Angers, 49933 - Angers/FR
  • 14 Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 15 Medical Oncology, Clinique de l'Estuaire, 44606 - Saint-Nazaire/FR
  • 16 Clinical Research Unit, IFCT, 75009 - PARIS/FR
  • 17 Clinical Research Unit, French Cooperative Thoracic Intergroup, 75009 - Paris/FR
  • 18 Pneumologie, CHU Grenoble, 38700 - La Tronche/FR
  • 19 Pulmonology And Thoracic Oncology, CHU Lille, Inserm, U1189 - ONCO-THAI - F-59000, 59000 - Lille/FR


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Abstract 5378


The phase IIR trial IFCT-1501 (MAPS2) tested nivo or nivo+ipi in pts with relapsed MPM as second/third-line. This trial reached its primary endpoint with 40% or more of pts with disease control in both arms. We now focus on long-term survivals and specific patterns of progression.


125 pts were randomized to receive Nivo 3 mg/kg q2w or Nivo 3 mg/kg q2w+Ipi 1mg/kg q6w, until progr or unacceptable toxicity. Median follow-up for OS is 32.5 months (Mar. 1st2019). HPD was defined by calculating the tumor growth rate before and during i.o. with determining the variation per month (ΔTGR) (Ferrara, JAMA Oncol 2018) or by measuring the tumor growth kinetics (TGK)on i.o. and on last treatment before, with TGK ratio (TGKr) calculation (Saâda-Bouzid, Ann. Oncol. 2017). HPD was defined as disease progression (assessed by BICR) with ΔTGR exceeding 50% or with a TGKr>2.


Median OS was 11·9 mo. (6·7–17·4) in the nivo arm and 15·9 mo. (10·7–22.2) in the nivo+ipilimumab arm. 52 (82%) /63 pts in the nivo group and 49 (79%)/62 patients in the combo group had died by data cutoff. 1 & 2-year survivals were 49·2% (36·4–60·8) & 25·4% (15·5–36·6) in the nivo arm, and 58·1% (44·8–69·2) & 31·7% (20·5–43·4) in the Nivo +Ipi arm. With ΔTGR method, 4 and 2 patients in Nivo and combo group had HPD respectively, while 7 and 4 patients had HPD by using TGKr. HPD pts with TGKr had a poorer OS than pts with standard progression only in the nivolumab arm (median OS = 1.6 mo [0.8-7.7] vs. 4.4 mo [2.4-10.8], (p = 0.02 in Cox model), while no difference was seen with ΔTGR definition.When both arms were analyzed together, only HPD pts defined with the TGKr had significantly worse survival: HR (progressive pts vs HPD): 0.37 [0.19-0.75], p = 0.006, with HR (pts with DCR vs. HPD)= 0.12 [0.06-0.25], p < 0.0001 and 2.6, 5.5 and 23.1 mos of median OS for HPD, progressive and pts with DCR respectively. All HPD patients with available IHC data (n = 8/11) had PDL1-neg expression at 1% cut-off (p = 0.001).


The durable efficacy of Nivo & Nivo+Ipi in MPM in confirmed, with 1/4 and 1/3 of pts alive at 2 yrs respectively. HPD pattern of progression did exist in both arms, associated with significantly worse survival when the TGKr definition of HPD is used.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

IFCT: French Cooperative Thoracic Intergroup.




G. Zalcman: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Inventiva; Honoraria (self), Advisory / Consultancy: Merck (MSD); Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche-France; Travel / Accommodation / Expenses: AbbVie. J. Mazieres: Honoraria (institution), Research grant / Funding (self): Roche-France; Honoraria (institution): BMS; Honoraria (institution), Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. L. Greillier: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Non-remunerated activity/ies: Novartis; Honoraria (self), Non-remunerated activity/ies: Lilly; Honoraria (self), Non-remunerated activity/ies: Pfizer; Honoraria (self), Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Boerhinger-Ingelheim; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: MSD. S. Lantuejoul: Honoraria (self), Non-remunerated activity/ies: MSD; Honoraria (self), Non-remunerated activity/ies: Roche-Diagnostics; Honoraria (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: BMS. O. Bylicki: Honoraria (self), Non-remunerated activity/ies: MSD; Non-remunerated activity/ies: Roche. I. Monnet: Travel / Accommodation / Expenses: BMS. R. Corre: Advisory / Consultancy: Roche; Advisory / Consultancy: BMS. C. Audigier-Valette: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Boerhinger-Ingelheim; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): Sysmex; Honoraria (self): MSD; Honoraria (self): Clovis Oncology; Honoraria (self): AbbVie. O. Molinier: Honoraria (self): BMS. F. Guisier: Honoraria (self), Non-remunerated activity/ies: 3MS; Honoraria (self): MSD US; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self), Research grant / Funding (self): Boerhinger-Ingeheim; Non-remunerated activity/ies: Chugai. D. Planchard: Honoraria (self): AstraZeneca; Honoraria (self): Boerhinger Ingelheim; Honoraria (self): BMS; Honoraria (self): Celgene; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Roche. E. Amour: Full / Part-time employment: IFCT. F. Morin: Full / Part-time employment: IFCT. D. Moro-Sibilot: Honoraria (self), Non-remunerated activity/ies: BMS; Honoraria (self): Roche; Honoraria (self): MSD; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Boerhinger Ingelheim; Honoraria (self): Takeda; Honoraria (self): Leurquin Mediolanum. A. Scherpereel: Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self): MSD; Honoraria (self): Boerhinger Ingelheim. All other authors have declared no conflicts of interest.

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