. 2020 Jul 26;44(3):260–271. doi: 10.1016/j.bj.2020.07.009

Table 1.

Outcomes in cancer patients treated by immunotherapy: studies including age group comparisons.

Publication (author, journal, year and study type)	Reference number	Immunotherapy (ies) used	Tumor localisation(s)	Immunotherapy arm	Elderly population		ORR	Overall survival (patients receiving immunotherapy)		Progression free or recurrence free survival		Toxicity (grade 3-4 adverse events unless specified any grades)		Statistical effect on clinical outcome	Conclusion
Publication (author, journal, year and study type)	Reference number	Immunotherapy (ies) used	Tumor localisation(s)	n=	Age groups	n=	ORR	Median or HR	Statistical difference	Median or HR	Statistical difference	Median or HR	Statistical difference	Statistical effect on clinical outcome	Conclusion
Elkrief A, J Geriatr Oncol, 2020, retrospective, real life and multicentric cohort	70	Anti-PD-1 and anti-PD-L1 nivolumab, pembrolizum and others	NSCLC	381	<70	257		13,7 months	p = 0,23	3,2 months	p = 0,92	6%		no age interaction with the clinical outcome	No difference according to age groups
	70	Anti-PD-1 and anti-PD-L1 nivolumab, pembrolizum and others	NSCLC	381	≥70	124		11,6 months		4,3 months		5%		no age interaction with the clinical outcome	No difference according to age groups
Borghaei H, NEJM, 2015, clical trial versus docetaxel, subgroup analysis	72	Nivolumab	NSCLC	582	<65	339		HR = 0,81							OS comparable in the 65-75 but less better in the ≥ 75 years old group
					65–75	200		HR = 0,63
					≥75	43		HR = 0,9
Brahmer J, NEJM, 2015, clical trial versus docetaxel, subgroup analysis	73	Nivolumab	NSCLC	135	<65	79		HR = 0,52							OS worse in the ≥75 years old group
					65–75	45		HR = 0,56
					>75	11		HR = 1,85
Gettinger SN, JCO, 2015, phase 1	76	Nivolumab	NSCLC	129	<70	90	16.7%								Similar ORR in age groups
Gettinger SN, JCO, 2015, phase 1	76	Nivolumab	NSCLC	129	≥70	39	17.9%								Similar ORR in age groups
Spigel D, J Thor oncol, 2019, phase 3–4b	77	Nivolumab	NSCLC	1426	<70	870		10,3 months		60%		12%	p = ns	ECOG PS = 2 had shorter OS	No difference according to age groups
					≥70	556						14%			No difference according to age groups
					whole	1426		9,1 months		62%					ECOG geriatric score impacts OS
Grossi F, Eur J Cancer 2018, multicentric real-world study	78	Nivolumab	NSCLC	371	<65	126	18%	8,6 months		4 months	ns	3%			No difference in <65 and 65–75 years of age
					65–75	175	18%	8 months		4,5 months		9%
					≥75	70	19%	5,8 months		3,2 months		3%
					whole	371	18%	7,9 months		4,2 months		6%			OS/PFS worse in the ≥ 75 years old group
Landre T, JCO, 2016, sub-group analysis of pooled published randomized control trials versus standard therapy	71	Nivolumab	NSCLC & RCC	687	65–75	541		HR = 0.6	p < 0.0001	HR = 0.78	p = 0.06			age effect depending on the age group	Immunotherapy better than standard therapy in 67–75 but not if ≥ 75 years old
	71	Nivolumab	NSCLC & RCC	687	≥75	146		HR = 1.22	p = 0.36	HR = 1.24	p = 0.43			age effect depending on the age group
Motzer RJ, NEJM, 2015, phase 3 versus everolimus	74	Nivolumab	RCC	410	<65	257		HR = 0,78							OS comparable in the 65–75 but worse in the ≥75 years old group
					65–75	119		HR = 0,64
					≥75	34		HR = 1,23
Motzer RJ, NEJM, 2018, phase 3 versus sunitinib	74	Nivolumab + ipilimumab	RCC	425	<65	265		HR = 0,53							OS better in the 65–75 but worse in the ≥ 75 years old group compare to sunitinib
					65–75	125		HR = 0,86
					≥75	35		HR = 0,97
Ferris RL, NEJM, 2007, phase 3 versus standard chemotherapy	75	Nivolumab	Head and neck	228	<65	172		HR = 0,64							OS worse in the 65–75 years old group
Ferris RL, NEJM, 2007, phase 3 versus standard chemotherapy	75	Nivolumab	Head and neck	228	65–75	56		HR = 0,93							OS worse in the 65–75 years old group
Balar AV, lancet oncol, 2017, multicentre phase 2, subgroup analysis	83	Pembrolizumab	Bladder	370	<65	57	30%							in PD-L1>10%, worse ORR in elderly	Similar ORR in age grops
	83	Pembrolizumab	Bladder	370	≥65	25	26%							in PD-L1>10%, worse ORR in elderly	Similar ORR in age grops
Bellmunt J, NEJM, 2017, phase 3 versus chemotherapy, subgroup analysis	84	Pembrolizumab	Bladder	270	<65	105		HR = 0,75							Similar ORR in age grops
	84	Pembrolizumab	Bladder	270	≥65	165		HR = 0,76							Similar ORR in age grops
Betof AS, the oncologist, 2017, retrospective, 2 centers	79	Anti-PD-1 and anti-PD-L1	Melanoma	254	<50	57		22,9 months	ns HR = 0,93	4,1 months	ns HR = 0,98	any 38,6%			No difference according to age groups
					50–64	85		25,3 months	ns HR = 0,88	6,5 months	ns HR = 0,82	43.50%
					65–74	65		22 months	ns HR = 0,83	5,4 months	ns HR = 0,85	49.20%
					>75	47	1	24,3 months	HR = 1	7,9 months	HR = 1	40.40%
Rai R, annal oncol, 2016, retrospective and multicentric analysis	80	Pembrolizumab and nivolumab	Melanoma	283	≤75	256	34%	48,1 months	p = ns	4,6 months	p = ns	any 37%	p = ns		No difference according to age groups
	80	Pembrolizumab and nivolumab	Melanoma	283	>75	35	48%	33,5 months		8,7 months		40%			No difference according to age groups
Robert C, NEJM, 2015, phase 3 versus dacarbazine, subgroup analysis	81	Nivolumab	Melanoma	210	<65	106		HR = 0,52							OS similar in the 65–75 and better in the ≥75 years old group compare to sunitinib
					65–75	77		HR = 0,44
					>75	27		HR = 0,25
Chiarion Sileni V, J Exp Clin Cancer Res, 2014, multicentric pooled analysis	82	Ipilimumab	Melanoma	833	≤70	645		3,7 months	p = 0,17	7 months	p = 0,33	any 36%	p = ns		No difference according to age groups
	82	Ipilimumab	Melanoma	833	>70	188		4 months		8,9 months		any 33%			No difference according to age groups
Kugel CH, clin cancer research, 2018, restrospective multicentric + preclinical model	88	Pembrolizumab	Melanoma	538	<62	238				progression 48%	p = 0,02				Probability of progression significantly decreases with age
	88	Pembrolizumab	Melanoma	538	≥62	300				37%					Probability of progression significantly decreases with age

Abbreviations: HR: hazard ratio; ns: non significant; NSCLC: non small cell lung cancer; OS: overall survival; ORR: overall response rate; RCC: renal cell carcinoma.