Table. Hazard Ratios Estimated Using the FPCM and the Classic Cox Proportional Hazards Regression Model.

Trial	Experimental vs standard comparison	Hazard ratio (95% CI)		FPCM P valueb		PFS of non–long-term responders in FPCM	Source
		Cox proportional hazards regression	FPCMa	LRF effect	Short-term effect
Melanoma: first-line treatment
CheckMate-066	Nivolumab vs dacarbazine	0.41 (0.32-0.52)	0.40 (0.32-0.51)	<.001	NA	SFT	Ascierto et, 201930
CheckMate-067	Nivolumab vs ipilimumab	0.59 (0.49-0.71)	Time varying	<.001	<.001	SDE	Wolchok et al, 201731
		0.56 (0.46-0.67)	Time varying	<.001	<.001	SDE	Hodi et al, 20187
		0.61 (0.51-0.74)	Time varying	<.001	<.001	SDE	Larkin et al, 201932
	Nivolumab plus ipilimumab vs ipilimumab alone	0.43 (0.35-0.53)	Time varying	<.001	<.001	SDE	Wolchok et al, 201731
		0.40 (0.33-0.49)	0.40 (0.33-0.49)	<.001	NA	SFT	Hodi et al, 20187
		0.41 (0.33-0.49)	0.41 (0.33-0.49)	<.001	NA	SFT	Larkin et al, 201932
Melanoma: first line or later
Intergroup trial E1690	10 mg/kg vs 3 mg/kg of ipilimumab	0.86 (0.74-1.01)	0.87 (0.75-1.02)	.09	NA	NS	Ascierto et al, 201733
Keynote-006	Pembrolizumab every 2 weeks vs ipilimumab	0.57 (0.46-0.69)	0.57 (0.47-0.69)	<.001	NA	SFT	Robert et al, 20191
	Pembrolizumab every 3 weeks vs ipilimumab	0.57 (0.47-0.70)	0.57 (0.47-0.70)	<.001	NA	SFT
Melanoma: second line or later
CheckMate-037	Nivolumab vs ICC	0.78 (0.59-1.02)	Time varying	.03	<.001	SDE	Larkin et al, 201834
CA184-002	Ipilimumab plus GP100 vs GP100	0.85 (0.69-1.03)	0.84 (0.68-1.02)	.08	NA	SFT	Hodi et al, 201035
NSCLC: first-line treatment
CA184-104	Ipilimumab plus chemotherapy vs chemotherapy	0.90 (0.77-1.05)	0.90 (0.77-1.05)	.18	NA	NS	Govindan et al, 201736
CheckMate-227 PDL1 ≥ 1%	Nivolumab plus ipilimumab vs chemotherapy	0.82 (0.70-0.98)	Time varying	<.001	<.001	SDE	Hellman et al, 201937
	Nivolumab plus ipilimumab vs nivolumab	0.83 (0.71-0.98)	0.83 (0.71-0.98)	.02	NA	SFT
CheckMate-227	Nivolumab plus ipilimumab vs chemotherapy	0.78 (0.61-0.99)	Time varying	<.001	<.001	SDE
PDL1 < 1%	Nivolumab plus ipilimumab vs nivolumab plus chemotherapy	1.00 (0.79-1.27)	Time varying	.06	<.001	SDE
	Nivolumab plus chemotherapy vs chemotherapy	0.71 (0.56-0.90)	0.72 (0.57-0.91)	.007	NA	SFT
NSCLC: second line
CheckMate-017	Nivolumab vs docetaxel	0.64 (0.49-0.84)	0.64 (0.49-0.83)	<.001	NA	SFT	Horn et al, 20172
		0.65 (0.50-0.85)	Time varying	<.001	.009	SDE	Antonia et al, 201920
CheckMate-057	Nivolumab vs docetaxel	0.92 (0.77-1.11)	Time varying	.004	<.001	SDE	Horn et al, 20172
		0.93 (0.77-1.11)	Time varying	<.001	<.001	SDE	Antonia et al, 201920
NSCLC: second line or later
OAK	Atezolizumab vs docetaxel	0.98 (0.87-1.11)	Time varying	<.001	<.001	SDE	Fehrenbacher et al, 201838

Abbreviations: CA184-002, MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma; CA184-104, Phase 3 Trial in Squamous Non Small Cell Lung Cancer Subjects Comparing Ipilimumab Vs Placebo in Addition to Paclitaxel and Carboplatin; CheckMate-017, Study of BMS-936558 [Nivolumab] Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell NSCLC; CheckMate-037, A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy; CheckMate-057, Study of BMS-936558 [Nivolumab] Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC; CheckMate-066, Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma; CheckMate-067, Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma; E1690, Phase 3 Trial in Subjects With Metastatic Melanoma Comparing 3 mg/kg Ipilimumab Versus 10 mg/kg Ipilimumab; FPCM, flexible parametric cure model; GP100, glycoprotein 100; ICC, investigator choice chemotherapy; Keynote-006, Study of Pembrolizumab [MK-3475] in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non–Small Cell Lung Carcinoma; LRF, long-term responder fraction; NA, not applicable; NS, nonsignificant; NSCLC, non–small cell lung cancer; OAK, Study of Atezolizumab Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum-Containing Therapy; PDL1, programmed cell death ligand 1; PFS, progression-free survival; SDE, significantly deleterious effect of the experimental treatment during early time points followed by a significant beneficial effect (direction of the effect varies over time); SFT, significantly in favor of the experimental treatment.

^a For models with time-dependent effects, a single hazard ratio may not provide a relevant measure of the treatment effect.

^b Treatment effect on the LRF was only tested for models with time-varying effects.