Table 3.
Studies on effect of body composition on tumor response and survival in patients with stage IV non-small cell lung cancer treated with immune checkpoint inhibitors.
| Publication | Sample Size | Male, % | Number of PD-L1 Positive Patients | Immune Checkpoint Inhibitor | Surrogate for Body Composition | Cut-off for Surrogate | End Point | Results* | P-Value |
|---|---|---|---|---|---|---|---|---|---|
| Kichenadasse et al. (52) | 1434 | 890 (62) | 938 ** | Atezolizumab | BMI | Per WHO Class | OS | Obesity vs. normal weight. HR 0.64 [CI 95%, 0.51-0.81] |
P < 0.001 |
| PFS | Overweight and obese vs. normal weight HR 0.88 [CI 95%, 0.78-0.99] |
P = 0.03 | |||||||
| Cortellini et al. (105) | 976 total with 635 NSCLC cases | 663 (67.9) | NA | Pembrolizumab, Nivolumab, Atezolizumab | BMI | Overweight/ obese >= 25 vs. non-overweight <25 | ORR | 41.3 % vs 20.9% | P < 0.0001 |
| TTF | 9.3 [95% CI: 8.1-11.6] vs 3.6 [95% CI: 3.2 - 4.1] months HR= 0.51 [95% CI: 0.44 – 0.60] |
P < 0.0001 | |||||||
| PFS | 11.7 [95% CI: 9.4 – 15] vs 3.7 [95% CI: 3.2 – 4.1] months HR= 0.46 [95%CI: 0.39 – 0.54] |
P < 0.0001 | |||||||
| OS | 26.6 [95% CI: 21.4 – 36.8] vs 6.6 [95% CI: 5.8 – 8.5] months HR= 0.33 [95%CI: 0.28 – 0.41] |
P < 0.0001 | |||||||
| Ichihara et al. (106) | Cohort 1: 84 | 68 (80.9) | 84 *** | Pembrolizumab | BMI | 22 | ORR | (evaluated in 74 pts.) 0% complete response 44.6% -partial response, 32.4%- stable disease, 23%- progressive disease |
|
| PFS | 7.3 vs. 4.7 months (HR): 0.94; 95 % CI: 0.53–1.65 |
P = 0.84 | |||||||
| OS | NR vs. 17 months HR: 0.67; 95 % CI: 0.32–1.40 |
P = 0.29 | |||||||
| Cohort 2: 429 | 338 (78.7) | 45 | Pembrolizumab, Nivolumab, Atezolizumab | ORR | (evaluated 403 pts.) 1.5% complete response, 23.3% partial response, 36.2% stable disease, 3% progressive disease |
||||
| PFS | 3.7 vs 2.8 months HR: 0.79; 95 % CI: 0.64–0.98 |
P = 0.036 | |||||||
| OS | 15.4 vs 13.5 months HR: 0.73; 95 % CI: 0.57–0.95 |
P = 0.021 | |||||||
| High PDL-1 and High BMI vs Low PDL-1 and Low BMI | PFS: 17 vs 3.5 months | P = 0.007 | |||||||
| OS: NR vs 16.1 months | P = 0.031 | ||||||||
| Magri et al. (107) | 46 | 28 (60.87) | NA | Nivolumab | Weight loss | Weight loss > 5% prior to therapy vs weight loss <5% | OS | 2 vs 10 months | P = 0.0076 |
| Popinat et al. (31) | 55 | 41 (75) | 13 **** | Nivolumab | SCFM | 5 kg/m2 | 1-year OS | HR: 0.75 | P = 0.006 |
| Minami et al. (108) | 74 | 48 (64.8) | 28 ***** | Nivolumab, Pembrolizumab, Atezolizumab | BMI, | BMI cutoff point 18.5 Higher BMI vs lower BMI |
OS | 15.8 vs. 3.3 months HR = 1.83 (0.79 - 4.21) |
P < 0.01 |
| PFS | No significant difference | - | |||||||
| IMAC | Men: 0.358 Women: 0.229 | OS | Low IMAC favorable for OS (HR 0.43, 95% CI 0.18 - 0.998) | P = 0.0496 | |||||
| PFS | No significant difference | - | |||||||
| Shiroyama et al. (39) | 42 | 26 (61.9) | NA | Nivolumab, Pembrolizumab | PMI Sarcopenia vs non-sarcopenia | Male: 6.36 cm2/m2 Female: 3.92 cm2/m2 | PFS | 2.1 vs 6.8 months | P= 0.004 |
| Overall response rate | 9.1 % vs. 40% | P = 0.025 | |||||||
| Nishioka et al. (109) | 38 | 26 (68.4) | 16 **** | Nivolumab, Pembrolizumab | Psoas Muscle Major Area change Sarcopenia vs non-sarcopenia |
Change of equal or more than 10% | ORR | 0 % versus 41% | P = 0.0154 |
| PFS | 47 vs. 204 days [CI 23-76] vs [CI 59-NA] | P = 0.00186 | |||||||
| Katayama et al. (110) | 35 | 24 (68.6) | 22**** | Pembrolizumab, Nivolumab, Atezolizumab | BMI | >20 | PFS | HR 0.43 [CI 95%, 0.19-0.95] | P = 0.036 |
| OS | No significant findings | - | |||||||
| Tsukagoshi etr al. (111) | 30 | 23 (76.7) | NA | Nivolumab | SMI | Male: 6.36 cm2/m2. Female 3.92 cm2/m2 | PFS | 7.5 vs 2.8 months | P = 0.008 |
| OS | 25 vs. 10 months | P = 0.03 | |||||||
| Partial response | 35.3% vs 0% | P = n/a | |||||||
| Roch et al. (112) | 142 | 93 (65.5) | 56 *** This cut off was only for those with pembrolizumab as first line | Pembrolizumab, Nivolumab | SMI Sarcopenia vs no-sarcopenia |
Male: 52.4 cm2/m2 Female: 38.5 cm2/m2 | PFS | 2.3 vs 4.1 months | P = 0.56 |
| OS | 7.6 vs. 12.6 months | P = 0.08 | |||||||
| Evolving Sarcopenia | (SMI) loss of ≥ 5%. Similar to definition of cachexia | PFS | 2.3 vs 5.1 months | P = 0.04 | |||||
| OS | 11.2 vs 15.2 months | P = 0.07 | |||||||
| Takada et al. (113) | 103 | 84 (81.6) | 25*** | Nivolumab, pembrolizumab | SMI Low SMI vs. high SMI |
Male: 25.63 cm2/m2 Female: 21.73 cm2/m2 | PFS | HR 1.6 [CI 95%, 1.02- 2.50] | P = 0.0399 |
| OS | HR 2.04 [CI 95%, 1.14- 3.63 | P = 0.0155 | |||||||
| BMI (univariate analysis) | Male: 21.9 Female 19.8 | PFS | Not significant HR 1.20 (0.78–1.86) | P = 0.4047 | |||||
| OS | HR 1.88 (1.09–3.27) | P = 0.0243 | |||||||
| RR | No effect of SMI or BMI on response rate | P = 0.0117 |
* Results reported comparing the higher than cut point group to the lower than cut point group; results are reported as either median PFS, OS or hazard ratios with confidence intervals.
** PD-L1 positivity identified by ≥5%
*** PD-L1 positivity identified by ≥ 50%
**** PD-L1 >1%
***** Tumor proportion score > 1%
Results are reported across different tumor types of which the majority were non-small cell lung cancer.
BMI, body mass index; CI, confidence interval; HR, hazard ratio; IMAC, Intermuscular adipose content; NA, not available; NR, not reached; PD-L1, programmed death-ligand-1; PFS, progression free survival; PMI, psoas muscle index; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; SMI, skeletal muscle index; SCFM, sub-cutaneous fat mass; TTF, time to treatment failure; WHO, world health organization.