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Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer

Adrien Costantini, Jennifer Corny, Vincent Fallet, Sophie Renet, Sylvie Friard, Christos Chouaid, Boris Duchemann, Etienne Giroux-Leprieur, Laurent Taillade, Ludovic Doucet, Marina Nguenang, Stéphane Jouveshomme, Marie Wislez, Jean Tredaniel, Jacques Cadranel
ERJ Open Research 2018 4: 00120-2017; DOI: 10.1183/23120541.00120-2017
Adrien Costantini
1Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC-04 Theranoscan, Paris, France
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Jennifer Corny
2Hôpital Saint-Joseph, Paris, France
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Vincent Fallet
1Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC-04 Theranoscan, Paris, France
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Sophie Renet
2Hôpital Saint-Joseph, Paris, France
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Sylvie Friard
3Hôpital Foch, Suresnes, France
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Christos Chouaid
4Centre Hospitalier Intercommunal de Créteil, Créteil, France
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Boris Duchemann
5Hôpital Avicenne, Bobigny, France
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Etienne Giroux-Leprieur
6Hôpital Ambroise Pare, Boulogne-Billancourt, France
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Laurent Taillade
7Hôpital Pitié-Salpêtrière, Paris, France
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Ludovic Doucet
8Hôpital Saint-Louis, Paris, France
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Marina Nguenang
9Hôpital Bichat and Université Paris-Diderot, Paris, France
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Stéphane Jouveshomme
2Hôpital Saint-Joseph, Paris, France
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Marie Wislez
1Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC-04 Theranoscan, Paris, France
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Jean Tredaniel
2Hôpital Saint-Joseph, Paris, France
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Jacques Cadranel
1Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC-04 Theranoscan, Paris, France
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Figures

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  • FIGURE 1
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    FIGURE 1

    Study flow chart.

  • FIGURE 2
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    FIGURE 2

    Kaplan–Meier survival curves showing nivolumab a) overall survival and b) progression-free survival in all patients.

  • FIGURE 3
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    FIGURE 3

    Kaplan–Meier survival curves showing a) overall survival and b) progression-free survival in patients receiving post-nivolumab treatment.

  • FIGURE 4
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    FIGURE 4

    Swimmer plots showing post-nivolumab progression-free survival for the three main drugs studied according to the line of treatment in which they were received. a) Gemcitabine; b) docetaxel; c) erlotinib.

Tables

  • Figures
  • Supplementary Materials
  • TABLE 1

    Clinical and pathological baseline characteristics (all patients)

    Subjects303
    Age at nivolumab initiation years65 (17–91)
    Sex
     Male208 (69)
     Female95 (31)
    Smoking history
     Never-smoker23 (8)
     Current or ex-smoker278 (92)
     Missing data2 (1)
    Histology on initial biopsy
     Adenocarcinoma186 (61)
     Squamous cell carcinoma86 (28)
     Giant cell carcinoma20 (7)
     Sarcomatoid carcinoma4 (1)
     Adenosquamous carcinoma3 (1)
     Muco-epidermoid carcinoma2 (1)
     Undifferentiated EBV-linked carcinoma1 (<1)
     Missing1 (<1)
    Mutational status
     EGFR10 (3)
     KRAS50 (17)
     ALK2 (1)
     BRAF7 (2)
     Wild-type219 (72)
     Other15 (5)
    Stage at diagnosis
     Stage I–II30 (10)
      Post-operative recurrence26 (87)
     Stage III–IV273 (90)
    Lines of therapy before nivolumab2 (0–9)
     01 (<1)
     1120 (40)
     288 (29)
     ≥394 (31)
    Performance status at nivolumab initiation
     059 (19)
     1145 (48)
     260 (20)
     37 (2)
     42 (1)
     Missing30 (10)
    Metastatic sites at nivolumab initiation
     Lung120 (40)
     Pleura88 (29)
     CNS62 (20)
     Liver48 (16)
     Adrenal glands54 (18)
     Bone78 (26)
    PD-L1 status determined by IHC120 (40)
     Positive (>1%)31 (10)
     Negative32 (11)
     Not performed240 (79)

    Data are presented as n, median (range) or n (%). EBV: Epstein–Barr virus; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase; CNS: central nervous system; PD-L: programmed death ligand; IHC: immunohistochemistry.

    • TABLE 2

      Clinical and pathological baseline characteristics of patients eligible for post-nivolumab treatment

      Did not receive further chemotherapyReceived further chemotherapyp-value
      Patients76 (40)115 (60)
      Age at nivolumab initiation65.5 (34–86)63 (17–84)0.11
      Sex0.78
       Male52 (68)76 (66)
       Female24 (32)39 (34)
      Smoking history0.69
       Never-smoker6 (8)10 (9)
       Current or ex-smoker68 (89)104 (90)
       Missing data 2 (3)1 (1)
      Histology on initial biopsy0.91
       Adenocarcinoma46 (61)72 (63)
       Squamous cell carcinoma22 (29)30 (26)
       Other8 (11)13 (11)
      Stage at diagnosis0.57
       I–II7 (9)8 (7)
       III–IV69 (91)107 (93)
      Lines of therapy before nivolumab0.68
       01 (1)0 (0)
       130 (39)43 (37)
       223 (30)34 (30)
       ≥322 (29)38 (33)
      Performance status at nivolumab initiation0.028
       010 (13)28 (24)
       135 (46)61 (53)
       221 (28)15 (13)
       31 (1)0 (0)
       40 (0)0 (0)
       Missing9 (12)11 (10)
      Metastatic sites at nivolumab initiation0.49
       Lung31 (41)48 (42)
       Pleura27 (36)36 (31)
       CNS13 (17)20 (17)
       Liver17 (22)13 (11)
       Adrenal glands19 (25)15 (13)
       Bone21 (28)26 (23)
      Number of nivolumab injections before progression580.001
      Performance status at first tumour evaluation<0.0001
       00 (0)23 (20)
       120 (26)41 (36)
       219 (25)21 (18)
       316 (21)7 (6)
       47 (9)0 (0)
       Missing14 (18)23 (20)

      Data are presented as n (%), median (range) or median, unless otherwise stated. n=191. CNS: central nervous system. Bold type represents statistical significance.

      • TABLE 3

        Drugs and drug regimens used

        Patients
        Drug regimens (n=25) 
         Docetaxel24 (21)
         Paclitaxel9 (8)
         Erlotinib17 (15)
         Vemurafenib1 (1)
         Gemcitabine26 (23)
         Vinorelbine8 (7)
         Pemetrexed6 (5)
         Afatinib3 (3)
         Abemaciclib1 (1)
         Platin docetaxel1 (1)
         Platin pemetrexed4 (3)
         Platin gemcitabine1 (1)
         Platin paclitaxel1 (1)
         Platin paclitaxel bevacizumab1 (1)
         Platin vinorelbine1 (1)
         Platin etoposide1 (1)
         Paclitaxel trastuzumab1 (1)
         Vinorelbin trastuzumab1 (1)
         Abemaciclib necitumumab1 (1)
         Pemetrexed bevacizumab1 (1)
         Paclitaxel bevacizumab2 (2)
         Pertuzumab afatinib1 (1)
         Paclitaxel erlotinib1 (1)
         Cytarabine1 (1)
         Everolimus1 (1)
        Drugs (n=18)
         Docetaxel25 (22)
         Paclitaxel15 (13)
         Erlotinib18 (16)
         Vemurafenib1 (1)
         Gemcitabine27 (23)
         Vinorelbine10 (9)
         Pemetrexed11 (10)
         Afatinib4 (3)
         Abemaciclib2 (2)
         Trastuzumab2 (2)
         Necitumumab1 (1)
         Bevacizumab4 (3)
         Vemurafenib1 (1)
         Pertuzumab1 (1)
         Etoposide1 (1)
         Platin10 (9)
         Everolimus1 (1)
         Cytarabine1 (1)

        Data are presented as n (%), unless otherwise stated.

        • TABLE 4

          Multivariate analysis of factors associated with post-nivolumab overall survival

          Multivariate analysis
          Hazard ratio (95% CI)p-value
          Sex (male versus female)0.92 (0.62–1.36)0.67
          Number of injections of nivolumab0.95 (0.00–0.997)0.036
          Performance status at nivolumab initiation (0–1 versus 2–4)0.999 (0.60–1.65)0.998
          Performance status at first tumour evaluation (0–1 versus 2–4)1.60 (0.97–2.65)0.065
          Post-nivolumab treatment (yes versus no)2.55 (1.68–3.89)<0.0001
          Histology (squamous versus nonsquamous)1.47 (0.96–2.27)0.079

          Bold type represents statistical significance.

          Supplementary Materials

          • Figures
          • Tables
          • Supplementary Material

            Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

            FIGURE S1 Kaplan-Meier survival curves comparing post-NivoOS in patients who received or who did not receive CT after nivolumab progression in the group of patients eligible do post-nivolumab treatment 00120-2017_figureS1

            FIGURE S2 Kaplan-Meier survival curves showing post-Nivo0S for gemcitabine, docetaxel and erlotinib 00120-2017_figureS2

            FIGURE S3 Kaplan-Meier survival curves showing post-NivoPFS for gemcitabine, docetaxel and erlotinib 00120-2017_figureS3

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          Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer
          Adrien Costantini, Jennifer Corny, Vincent Fallet, Sophie Renet, Sylvie Friard, Christos Chouaid, Boris Duchemann, Etienne Giroux-Leprieur, Laurent Taillade, Ludovic Doucet, Marina Nguenang, Stéphane Jouveshomme, Marie Wislez, Jean Tredaniel, Jacques Cadranel
          ERJ Open Research Apr 2018, 4 (2) 00120-2017; DOI: 10.1183/23120541.00120-2017

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          Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer
          Adrien Costantini, Jennifer Corny, Vincent Fallet, Sophie Renet, Sylvie Friard, Christos Chouaid, Boris Duchemann, Etienne Giroux-Leprieur, Laurent Taillade, Ludovic Doucet, Marina Nguenang, Stéphane Jouveshomme, Marie Wislez, Jean Tredaniel, Jacques Cadranel
          ERJ Open Research Apr 2018, 4 (2) 00120-2017; DOI: 10.1183/23120541.00120-2017
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