Table 2.
Overview of selected phase 2 or 3 CAC clinical trials where findings are published. Results from the latest phase are reported. mAb, Monoclonal antibody; NSCLC, non-small cell lung cancer; WL, weight loss; Hb, haemoglobin; CRP, C-reactive protein; LBM, lean body mass; CRC, colorectal cancer; OS, overall survival; HGS, handgrip strength; FACIT-F, Functional Assessment of Chronic Illness Therapy; VAS, visual analog scale; FAACT-ACS, Functional Assessment of Anorexia/Cachexia Therapy-Anorexia/Cachexia Subscale; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer
| Pathway | Intervention | Trial description | Primary endpoints | Primary results |
|---|---|---|---|---|
| Ghrelin | Ghrelin receptor agonist anamorelin (274) | Phase 3. Inoperable advanced NSCLC and CAC | Change in LBM (DEXA) and HGS over 12 weeks | Significant increases in LBM in ROMANA 1 and ROMANA 2. No difference in HGS |
| GDF-15 | Anti-GDF-15 mAb ponsegromab (89) | Phase 2. NSCLC, pancreatic cancer, or CRC with elevated serum GDF-15, CAC, ECOG 0–3 | Change in weight over 12 weeks | Significantly greater weight gain |
| JAK-STAT & Related | Anti-IL-6 mAb clazakizumab (235) | Phase 2. Incurable advanced NSCLC with WL>5% over 3 months, ECOG 0–3, Hb >7g/dl, CRP>10mg/L | Change in safety parameters (adverse events, lad safety tests) | Safe and well tolerated. Additional observations: stabilisation of LBM (DEXA) |
| Anti-IL-1α mAb MABp1 (87) | Phase 3. Advanced CRC, ECOG 1–2, either CAC or IL-6 ≥ 10pg/ml and either anorexia, fatigue, pain, emotional and social function | Composite of change in LBM (DEXA) ≥ 0kg or health status (EORTC-QLQ-C30) ≥ 2 symptoms stable or improved, over 8 weeks | Higher proportion of patients achieved primary endpoint | |
| Anti TNF-α infliximab (234) | Phase 2. Advanced incurable NSCLC, ECOG < 2 | Weight gain ≥ 10% | No significant improvements, trial closed early | |
| Anti TNF-α etanercept (85) | Phase 3. Incurable advanced malignancy, ECOG ≥ 2 and WL ≥ 2.27kg over 2 months or <20 calories/kg body weight/day, appetite concern | Weight gain ≥ 10% | No significant improvements | |
| Anabolic Agents | Selective androgen receptor modulator - Enobosarm (290) | Phase 2. Male (>45 years) and female (post-menopausal) with cancer, not obese and >2% WL in 6 months | Change in LBM from baseline at 113 days or end of study | Significant increase in LBM |
| Anabolic/anti-catabolic (β-adrenergi modulation) - Espindolol (291) | Phase 2. Advanced CRC or NSCLC and CAC | Rate of weight change over 16 weeks between high dose espindolol and placebo | Significant increase in rate of weight change | |
| Anti-psychotics | Olanzapine (295) | Phase 3. Advanced gastric, hepatopancreaticobiliary, or lung cancer. | >5% weight gain, appetite improvement (VAS, FAACT-ACS) | Significantly higher proportion of patients with weight gain and improvement in appetite |