Figures
- FIGURE 1
Study flow chart.
- FIGURE 2
Kaplan–Meier survival curves showing nivolumab a) overall survival and b) progression-free survival in all patients.
- FIGURE 3
Kaplan–Meier survival curves showing a) overall survival and b) progression-free survival in patients receiving post-nivolumab treatment.
- 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
- TABLE 1
Clinical and pathological baseline characteristics (all patients)
Subjects 303 Age at nivolumab initiation years 65 (17–91) Sex Male 208 (69) Female 95 (31) Smoking history Never-smoker 23 (8) Current or ex-smoker 278 (92) Missing data 2 (1) Histology on initial biopsy Adenocarcinoma 186 (61) Squamous cell carcinoma 86 (28) Giant cell carcinoma 20 (7) Sarcomatoid carcinoma 4 (1) Adenosquamous carcinoma 3 (1) Muco-epidermoid carcinoma 2 (1) Undifferentiated EBV-linked carcinoma 1 (<1) Missing 1 (<1) Mutational status EGFR 10 (3) KRAS 50 (17) ALK 2 (1) BRAF 7 (2) Wild-type 219 (72) Other 15 (5) Stage at diagnosis Stage I–II 30 (10) Post-operative recurrence 26 (87) Stage III–IV 273 (90) Lines of therapy before nivolumab 2 (0–9) 0 1 (<1) 1 120 (40) 2 88 (29) ≥3 94 (31) Performance status at nivolumab initiation 0 59 (19) 1 145 (48) 2 60 (20) 3 7 (2) 4 2 (1) Missing 30 (10) Metastatic sites at nivolumab initiation Lung 120 (40) Pleura 88 (29) CNS 62 (20) Liver 48 (16) Adrenal glands 54 (18) Bone 78 (26) PD-L1 status determined by IHC 120 (40) Positive (>1%) 31 (10) Negative 32 (11) Not performed 240 (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 chemotherapy Received further chemotherapy p-value Patients 76 (40) 115 (60) Age at nivolumab initiation 65.5 (34–86) 63 (17–84) 0.11 Sex 0.78 Male 52 (68) 76 (66) Female 24 (32) 39 (34) Smoking history 0.69 Never-smoker 6 (8) 10 (9) Current or ex-smoker 68 (89) 104 (90) Missing data 2 (3) 1 (1) Histology on initial biopsy 0.91 Adenocarcinoma 46 (61) 72 (63) Squamous cell carcinoma 22 (29) 30 (26) Other 8 (11) 13 (11) Stage at diagnosis 0.57 I–II 7 (9) 8 (7) III–IV 69 (91) 107 (93) Lines of therapy before nivolumab 0.68 0 1 (1) 0 (0) 1 30 (39) 43 (37) 2 23 (30) 34 (30) ≥3 22 (29) 38 (33) Performance status at nivolumab initiation 0.028 0 10 (13) 28 (24) 1 35 (46) 61 (53) 2 21 (28) 15 (13) 3 1 (1) 0 (0) 4 0 (0) 0 (0) Missing 9 (12) 11 (10) Metastatic sites at nivolumab initiation 0.49 Lung 31 (41) 48 (42) Pleura 27 (36) 36 (31) CNS 13 (17) 20 (17) Liver 17 (22) 13 (11) Adrenal glands 19 (25) 15 (13) Bone 21 (28) 26 (23) Number of nivolumab injections before progression 5 8 0.001 Performance status at first tumour evaluation <0.0001 0 0 (0) 23 (20) 1 20 (26) 41 (36) 2 19 (25) 21 (18) 3 16 (21) 7 (6) 4 7 (9) 0 (0) Missing 14 (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) Docetaxel 24 (21) Paclitaxel 9 (8) Erlotinib 17 (15) Vemurafenib 1 (1) Gemcitabine 26 (23) Vinorelbine 8 (7) Pemetrexed 6 (5) Afatinib 3 (3) Abemaciclib 1 (1) Platin docetaxel 1 (1) Platin pemetrexed 4 (3) Platin gemcitabine 1 (1) Platin paclitaxel 1 (1) Platin paclitaxel bevacizumab 1 (1) Platin vinorelbine 1 (1) Platin etoposide 1 (1) Paclitaxel trastuzumab 1 (1) Vinorelbin trastuzumab 1 (1) Abemaciclib necitumumab 1 (1) Pemetrexed bevacizumab 1 (1) Paclitaxel bevacizumab 2 (2) Pertuzumab afatinib 1 (1) Paclitaxel erlotinib 1 (1) Cytarabine 1 (1) Everolimus 1 (1) Drugs (n=18) Docetaxel 25 (22) Paclitaxel 15 (13) Erlotinib 18 (16) Vemurafenib 1 (1) Gemcitabine 27 (23) Vinorelbine 10 (9) Pemetrexed 11 (10) Afatinib 4 (3) Abemaciclib 2 (2) Trastuzumab 2 (2) Necitumumab 1 (1) Bevacizumab 4 (3) Vemurafenib 1 (1) Pertuzumab 1 (1) Etoposide 1 (1) Platin 10 (9) Everolimus 1 (1) Cytarabine 1 (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 nivolumab 0.95 (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 Material
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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
