Table 2.

Studies refuting the obesity paradox for cancer immunotherapy outcomes.

First author (Year)	Tumor type	Cohort size	Trial name or SOC	Obesity metric used	ICI used	Controlled prognostic factors	Outcomes
McQuade (34)	melanoma	117 females	retrospective analyses from 4 US and Australian centers	BMI: per WHO for NW, OVWT, OB. UWT excluded	anti-PD-1, anti-PD-L1, or anti-CTLA-4 + dacarbazine (chemotherapy)	age, AJCC & disease stage, LDH status, ECOG status	OB vs NW: trending worse PFS and no change in OS
Donnelly (37)	melanoma	423	prospective NYU Interdisciplinary Melanoma Cooperative Group	BMI: per WHO standards for UW, NW, OVWT, OB	anti-PD-1, anti-CTLA-4, or combination	1st versus 2nd+ line of therapy; age, gender, tumor stage, LDH, ECOG, # metastatic sites; mono vs combo therapy	All patients: OVWT and OB: no changes in PFS or OS. OVWT and OB: 2nd line+ ICI trended toward worse PFS and OS.
							OVWT and OB: trend toward worse PFS with anti-PD-1 alone
Rutkowski (41)	melanoma	688	retrospective; SOC 3 Italian and 2 Polish centers	BMI: per WHO standards for UW, NW, OVWT, OB	mixed ICIs	age, sex, first line ICI vs ICI sequencing, tumor mutation status, LDH, ECOG	BMI: no effect on PFS or OS for either 1st line ICI or ICI sequencing
Young (42)	Melanoma	287	Retrospective; SOC	BMI: NW, OVWT, OB or CT scan for TATI, SMD, SMG	mixed: anti-PD-1, anti-PD-L1 or anti-PD-1 + anti-CTLA-4	age, sex, stage, prior therapies	BMI: no effect on PFS or OS in total cohort or men or women analyzed separately.
							High TATI: worse PFS with no change in OS in total cohort.
							SMG: no effect on PFS or OS.
Di Filippo (43)	Melanoma	1214	French 26-center MelBase NCT02828202	BMI: per WHO standards for NW, OVWT, OB.	anti-PD-1 or anti-PD-1+anti-CTLA-4	Age, sex, ECOG, LDH, brain	BMI: no effect on PFS or OS or TRAEs.
				UWT excluded		metastases, tumor mutation status, # metastatic sites	Overall response rates did not differ across BMI categories.
Bergerot (44)	RCC	42	Retrospective	BMI: OVWT+OB vs NW+UW	anti-PD-1 or anti-PD-L1 or anti-PD-1+anti-CTLA-4	sex, race, IMDC score, histology	High BMI (OVWT +OB): trending worse OS (not sig.)
De Giorgi (45)	RCC	313	Italian Expanded Access Program	BMI: OVWT+ OB vs NW+UWT	only anti-PD-1 (nivolumab)	age, ECOG SII, NLR, PLR	NW+UWT: patients with SII ≥ 1375 had worse OS vs patients with low BMI + low SII or high BMI + low SII or high BMI + high SII
Boi (18)	RCC	72	Retrospective SOC only (2 US institutions)	BMI: OB vs OVWT+ NW.	anti-PD-1	age, sex, IMDC score, # prior therapies	OB vs OVWT+NW: decreased PFS and OS.
				UWT excluded			OVWT+OB vs NW: no change in PFS or OS
Khojandi (30)	Mixed tumor types	149	Retrospective SOC	BMI: OB vs OVWT+NW+UWT	anti-PD-1/PD-L1	sex	OB: no change in OS

For studies based upon the use of BMI as the obesity defining metric, UWT, underweight (BMI<18.5 kg/m²); NW, normal weight (BMI 18.5-24.9 kg/m²); OVWT, overweight (BMI 25-29.9 kg/m²); OB, obesity (BMI > 30 kg/m²). Note that non-significant data trends are indicated as such; all other outcomes listed are significant as per the original report. AJCC, American Joint Committee on Staging; CRP, C reactive protein; CT, computed tomography; ECOG, Eastern Cooperative Oncology Group performance status; irAEs, immune-related adverse events; LDH, lactate dehydrogenase; NLR, neutrophil to lymphocyte ratio; NR, not reported; NSCLC, non-small cell lung carcinoma; OS, overall survival; PFS, progression-free survival; PLR; platelet to lymphocyte ratio; RCC, renal cell carcinoma; SII, systemic inflammation index; SMD, smooth muscle density; SMG, smooth muscle gauge; SOC, standard of care; TATI, total adipose tissue index; TRAEs, treatment-related adverse events.