Table 2. . Design and patient characteristics of identified studies.
| Study | Patients | Previous treatment | Treatments | Efficacy and safety outcomes | QoL assessment | Ref. | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Experimental arm | Control arm | OS (months) | PFS (months) | Tolerability (most common adverse events) | Scale | Frequency of assessment | Outcomes | ||||
| LUME-Lung 1 | Unselected stage IIIB/IV NSCLC (all histologies) | Chemotherapy | Docetaxel + nintedanib | Docetaxel + placebo | 12.6 vs 10.3; p = 0.0359 (key secondary end point in adenocarcinoma patients) | 3.4 vs 2.7; p = 0.0019 | Grade ≥3: diarrhea (3.6 vs 2.6%); reversible increased ALT (7.8 vs 0.9%; reversible increased ALT (3.4 vs 0.5%) |
EORTC QLQ-LC13, EORTC QLQ-C30, EQ-5D and EQ-VAS | Baseline, end of every cycle, and end of therapy and at the first follow-up visit | TTD (first appearance of a minimal clinically important difference [≥10-point change]) and longitudinal assessment of cough, dyspnea and pain | [4,17] |
| CheckMate 017 | Stage IIIB/IV NSCLC (squamous cell histology) | Prior systemic therapies | Nivolumab | Docetaxel | 9.2 vs 6.0; p < 0.001 (primary end point) | 3.5 vs 2.8; p < 0.001 | Grade 3–4: neutropenia (0 vs 30%) | LCSS (ASBI and 3-Item Index), EQ-5D and EQ-VAS | Baseline, every 4 weeks (nivolumab arm) and every 3 weeks (docetaxel arm) for first 6 months | TTD, mean change in scores over time, LCSS ASBI improvement (≥10-point change) by week 12 | [13,16] |
| BR.21 | Unselected NSCLC (all histologies) | Chemotherapy (one or two lines) | Erlotinib | Placebo | 6.7 vs 4.7; p < 0.001 (primary end point) | 2.2 vs 1.8; p < 0.001 | All grades: rash (76 vs 17%); anorexia (69 vs 56%); stomatitis (19 vs 3%) | EORTC QLQ-LC13, EORTC QLQ-C30 | Baseline, every 4 weeks during treatment, 4 weeks after completing treatment and every 12 weeks thereafter until documentation of PD | TTD (first appearance of a minimal clinically important difference [≥10-point change]), cough, dyspnea and pain (primary outcome for QoL) Percentage improved/stable/worse |
[18,19] |
| JMEI | Advanced NSCLC (all histologies) | Chemotherapy | Pemetrexed | Docetaxel | 8.3 vs 7.9; p = NS (primary end point) | 2.9 vs 2.9 | Grade 3–4: neutropenia (5 vs 40%); febrile neutropenia (2 vs 13%) | LCSS (ASBI) | NR | Percentage of patients who were improved, stable or worse (or meaningful change) on ASBI (>0.5 SD change from baseline) or LCSS (1-point change) | [20,21] |
| TITAN | Advanced NSCLC (all histologies) | Platinum-based therapy | Erlotinib | Docetaxel/pemetrexed | 5.3 vs 5.5; p = 0.73 (primary end point) | 6.3 vs 8.6; p = 0.089 | All grades: rash (50 vs 5%); diarrhea (18 vs 2%); alopecia (0 vs 11%) | FACT-L, version 4 | Baseline, every 3 weeks until Week 48 and every 12 weeks thereafter until PD | TTP TTD |
[22] |
| TAILOR | Advanced, EGFR wild-type NSCLC (all histologies) | Platinum-based therapy | Erlotinib | Docetaxel | 5.4 vs 8.2; p = 0.05 (primary end point) | 2.4 vs 2.9; p = 0.02 | Grade 3–4: low absolute neutrophil count (0 vs 20%); skin toxic effects (14 vs 0%) and asthenia (6 vs 10%) | EORTC QLQ-LC13, EORTC QLQ-C30 | Baseline and before each treatment cycle | – | [14,15] |
| TAX-317 | Advanced IIIB/IV NSCLC (all histologies) | Chemotherapy | Docetaxel | Best supportive care | 7.0 vs 4.6; p = 0.047 (primary end point) | TTP (weeks): 10.6 vs 6.7; p < 0.001 | Grade 3 or 4 neutropenia: 86% (100 mg/m2) and 67% (75 mg/m2) | LCSS EORTC QLQ-LC13 |
Baseline, immediately before each treatment cycle, at the end of drug treatment and every 2 months during follow-up | Longitudinal analysis; mixed-model analysis and ANCOVA | [23,24] |
ANCOVA: Analysis of covariance; ASBI: Average symptom burden index; EORTC: European Organization for Research and Treatment of Cancer; EORTC QLQ-C30: EORTC multidimensional core questionnaire; EORTC QLQ-LC13: EORTC lung cancer questionnaire; EQ-5D: EuroQol-5D; EQ-VAS: EuroQol-visual analog scale; FACT-L: Functional Assessment of Cancer Therapy - Lung; LCSS: Lung Cancer Symptom Scale; NR: Not reported; NS: Not significant; OS: Overall survival; PD: Progressive disease; PFS: Progression-free survival; QoL: Quality of life; RR: Relative risk; SD: Standard deviation; TTD: Time to deterioration; TTP: Time to progression.