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Table 2 Summary of interventions that showed a significant (P < 0.05) benefit over single-agent docetaxel (75 mg/m2): fixed-effects NMA

From: Relative efficacy of interventions in the treatment of second-line non-small cell lung cancer: a systematic review and network meta-analysis

Histology

PD-L1 expression

EGFR mutation

Occurrence (Non-Asian)

Occurrence (Asian)

OS (Hazard ratio NMA)

PFS (Fractional polynomial NMA)

Non-squamous

<  5%

Negative

32.8%

21.2%

Docetaxel + nintedanib: 2.6 (0.1, 5.6)

Docetaxel + ramucirumab: 2.3 (0.3, 4.6)

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Squamous

<  5%

Negative

21.0%

20.2%

Nivolumab: 5.5 (0.7, 12.4)

Docetaxel + ramucirumab: 2.0 (0.3, 4.0)

Nivolumab: 2.6 (0.0, 5.8)a

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Non-squamous

≥ 5%

Negative

20.5%

13.3%

Nivolumab: 12.9 (5.6, 23.8)

Docetaxel + nintedanib: 2.6 (0.1, 5.6)

Docetaxel + ramucirumab: 2.3 (0.3, 4.6)

Nivolumab: 5.0 (2.2, 8.2)

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Squamous

≥ 5%

Negative

13.2%

12.7%

Nivolumab 8.0 (1.6, 17.8)

Docetaxel + ramucirumab: 2.0 (0.3, 4.0)

Nivolumab: 5.7 (1.8, 10.1)

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Non-squamous

<  5%

Positive

7.2%

18.8%

Docetaxel + erlotinib: 13.4 (4.8, 27.0)

Erlotinib + pemetrexed: 8.0 (0.3, 28.5)

Erlotinib: 7.4 (2.5, 14.9)

Gefitinib: 4.4 (0.8, 10.5)

Docetaxel + nintedanib: 2.6 (0.1, 5.6)

Docetaxel + ramucirumab: 2.3 (0.3, 4.6)

Docetaxel + erlotinib: 8.1 (4.9, 10.9)

Erlotinib + pemetrexed: 7.0 (1.2, 14.6)

Erlotinib: 6.8 (3.4, 11.3)

Gefitinib: 5.4 (2.7, 8.6)

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Squamous

<  5%

Positive

0.5%

1.3%

Docetaxel + erlotinib: 11.9 (4.2, 23.8)

Erlotinib: 6.5 (2.2, 13.2)

Nivolumab: 5.5 (0.7, 12.4)

Gefitinib: 3.9 (0.7, 9.3)

Docetaxel + ramucirumab: 2.0 (0.3, 4.0)

Docetaxel + erlotinib: 8.1 (4.9, 10.9)

Erlotinib: 6.8 (3.4, 11.3)

Gefitinib: 5.4 (2.7, 8.6)

Nivolumab: 2.6 (0.0, 5.8)a

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Non-squamous

≥ 5%

Positive

4.5%

11.8%

Docetaxel + erlotinib: 13.4 (4.8, 27.0)

Nivolumab: 12.9 (5.6, 23.8)

Erlotinib + pemetrexed: 8.0 (0.3, 28.5)

Erlotinib: 7.4 (2.5, 14.9)

Gefitinib: 4.4 (0.8, 10.5)

Docetaxel + nintedanib: 2.6 (0.1, 5.6)

Docetaxel + ramucirumab: 2.3 (0.3, 4.6)

Docetaxel + erlotinib: 8.1 (4.9, 10.9)

Erlotinib + pemetrexed: 7.0 (1.2, 14.6)

Erlotinib: 6.8 (3.4, 11.3)

Gefitinib: 5.4 (2.7, 8.6)

Nivolumab: 5.0 (2.2, 8.2)

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

Squamous

≥ 5%

Positive

0.3%

0.8%

Docetaxel + erlotinib: 11.9 (4.2, 23.8)

Nivolumab 8.0 (1.6, 17.8)

Erlotinib: 6.5 (2.2, 13.2)

Gefitinib: 3.9 (0.7, 9.3)

Docetaxel + ramucirumab: 2.0 (0.3, 4.0)

Docetaxel + erlotinib: 8.1 (4.9, 10.9)

Erlotinib: 6.8 (3.4, 11.3)

Nivolumab: 5.7 (1.8, 10.1)

Gefitinib: 5.4 (2.7, 8.6)

Docetaxel + ramucirumab: 1.2 (0.6, 1.9)

  1. Docetaxel = docetaxel (75 mg/m2) 3 times a week; difference in mean survival relative to docetaxel (75 mg/m2) after colon with 95% credible intervals in parentheses. Treatments shown in bold indicate relatively better performance in a group; (typically, the highest predicted mean survival) and performed better than one or more other treatments in the same group (P < 0.05). Occurrence of each tumor subgroup are only approximate and based on the following: 65% nonsquamous, 35% squamous [5]; non-Asian: 18% EGFR mutation positive in nonsquamous tumors; Asian: 47% EGFR mutation in nonsquamous tumors [76]; 8 times more likely to be EGFR positive if nonsquamous compared to squamous [77] and 38.5% PD-L1 ≥ 5% (combined data from Borghaei et al. [39]; Brahmer et al. [40]). Predictions from the NMA assumed relationships for each factor are the same across any other factor. This allowed predictions to be made across all subgroups, but where subgroups are rare, there may be little actual direct evidence for that patient population
  2. aBorderline significance (P = 0.0508)