Table 2.
Field testing of the ESMO-MCBS for the treatment of advanced lung cancer at the Medical University of Vienna
| Analysed treatment | Setting | Primary EP | PFS control | PFS gain | PFS HR | OS control | OS gain | OS HR | Adjustment/remark | MCBS | MCBS-FT |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Erlotinib vs carboplatin (OPTIMAL, CTONG 0802)* Zhou et al27 |
First-line IIIB or IV, non-squamous, EGFR-mutated | PFS | 4.6 m | 8.5 m | 0.16 (0.10 to 0.26) | – | – | – | 12% less serious AEs | 4 | NA |
| Erlotinib vs platinum-based CT doublet (EURTAC)* Rosell et al28 |
First-line IIIB or IV, non-squamous, EGFR-mutated | PFS | 5.2 m | 4.5 m | 0.37 (0.25 to 0.54) | 19.5 m | – | Non-significant | 15% less serious AEs | 4 | NA |
| Gefitinib vs Carboplatin+paclitaxel (IPASS) Mok et al29 Fukuoka et al30 |
First-line IIIB or IV, non-squamous (EGFR-mutated) |
PFS (all) PFS (EGFR+) |
NA 6.3 m |
NA 3.3 m |
0.74 (0.65 to 0.85) 0.48 (0.34 to 0.67) |
– – |
– – |
– – |
QOL improved, less toxicity | NA NA |
NA 4 |
| Afatinib vs cisplatin+pemetrexed (LUX Lung-3)* Sequist et al31 Yang et al32 Yang et al33 |
First-line IIIB or IV adenocarcinoma, EGFR-mutated (EGFR exon 19 deletion) | PFS (all) PFS (del19) |
6.9 m 6.9 m |
4.2 m 6.7 m |
0.58 (0.43 to 0.78) 0.47 (0.34 to 0.65) |
28.2 m 21.1 m |
– 12.2 m |
Non-significant 0.54 (0.36 to 0.79) |
OS improved for del19 patients | NA NA |
4 (4-)5† |
| Crizotinib vs CT* Shaw et al34 |
First-line IIIB or IV adenocarcinoma, ALK-mutated | PFS | 3.0 m | 4.7 m | 0.49 (0.37 to 0.64) | – | – | – | +1% toxic death, QOL improved | 4 | NA |
| Crizotinib vs cisplatin+pemetrexed* Solomon et al35 |
First-line IIIB or IV non-squamous, ALK-mutated | PFS | 7.0 m | 3.9 m | 0.45 (0.35 to 0.60) | – | – | – | QOL improved | 4 | NA |
| Cisplatin+pemetrexed vs cisplatin+gemcitabine* Scagliotiti et al36 |
First-line IIIB or IV non-squamous | Non-inferiority (OS) | – | – | – | 10.4 m | 1.4 m | 0.81 (0.70 to 0.94) | Less grade III haematologic AEs | 4 | NA |
| Paclitaxel/carboplatin±bevacizumab* Sandler et al37 |
First-line IIIB or IVB, non-squamous | OS | – | – | – | 10.3 m | 2.0 m | 0.79 (0.67 to 0.92) | 2 | NA | |
| Gemcitabine+cisplatin±bevacizumab (high/low dose) (AVAIL) Reck et al38 |
First-line advanced, non-squamous | PFS (low) PFS (high) |
6.1 m | 0.6 m 0.4 m |
0.75 (0.62 to 0.91) 0.82 (0.68 to 0.98) |
– | – | – | Survival data not mature | NA NA |
2 1 |
| CT±palliative care* Temel et al39 |
Stage IV, ECOG<2 | QOL | – | – | – | 8.9 m | 2.7 m | HR death 1.7 | QOL improved | 4 | NA |
| Pemetrexed vs placebo Ciuleanu et al40 |
Maintenance after response to platinum doublet (non-squamous) | PFS (all) PFS (non-sq.) |
2.6 m 2.6 m |
1.7 m 1.9 m |
0.50 (0.42 to 0,61) 0.44 (0.36 to 0.55) |
10.6 m 10.3 m |
2.8 m 5.2 m |
0.79 (0.65 to 0.95) 0.70 (0.56 to 0.88) |
NA NA |
3 4 |
|
| Erlotinib vs placebo (SATURN)* Capuzzo et al41 |
Maintenance after response to platinum doublet | PFS | 11.1 w | 1.2 w | 0.71 (0.62 to 0.82) | 11 m | 1.0 m | 0.81 (0.70 to 95) | 1 | NA | |
| Docetaxel±nintedanib (LUME-Lung1) Reck et al42 |
Second line (adenocarcinoma with PD 9 m after start first line) | PFS (all) PFS (adeno.) |
2.7 m 1.5 m |
0.7 m 2.1 m |
0.79 (0.68 to 0.92) 0.63 (0.48 to 0.83) |
9.1 m 7.9 m |
1.0 m 3 m |
0.94 (0.83 to 1.05) 0.75 (0.6 to 0.92) |
Uncertain significance of AEs, more diarrhoea | NA NA |
1 4 |
| Nivolumab vs docetaxel (Checkmate 057) Borghaei et al43 |
Second-line non-squamous cell lung cancer | OS | 4.2 m | – | – | 9.4 m | 2.8 m | 0.73 (0.59 to 0.89) | Significantly less grade III/IV toxicity | NA | 4 |
| Nivolumab vs docetaxel (Checkmate 017) Brahmer et al44 |
Second-line squamous cell lung cancer | OS | 2.8 m | 0.7 m | 0.62 (0.47 to 0.81) | 6.0 m | 3.2 m | 0.56 (0.44 to 0.79) | −48% grade III/IV AEs | NA | 5 |
Underlined words relate to the name of the trial/acronym.
*Adapted according to Cherny et al.8
†No quality-of-life data for overall survival available.
Adeno., adenocarcinoma only; AEs, adverse events; ALK, anaplastic lymphoma kinase; CT, chemotherapy; del, deletion; EP, end point; ESMO-MCBS, European Society for Medical Oncology Magnitude of Clinical Benefit Scale; ECOG, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; EGFR+, EGFR mutated only; FT, field testing; m, months; NA, not applicable; OS, overall survival; PD, progressive disease; PFS, progression-free survival; QOL, quality of life.