Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

Table 1 Comparison of the pivotal studies approving FOLFIRINOX and gemcitabine/nab-paclitaxel in metastatic pancreatic cancer

		ACCORD/PRODIGE trial (FOLFIRINOX )[9]	MPACT trial (GNP)[10]
Study characteristics	Duration	December 2005-October 2009	May 2009-April 2012
	Location	France	Multinational
	Number of patients	342	861
	Study design	Phase 2-3	Phase 3
	Control arm	Gemcitabine	Gemcitabine
Patient and tumor characteristics	Median age	61 years	62 years
	Sex distribution	Male (62%)	Male (57%)
	ECOG	PS 0 (37.4%)	KPS 100 (16%)
		PS 1 (61.9%)	KPS 80-90 (77%)
		PS 2 (0.6%)	KPS 60-70 (7%)
	Tumor stage	Metastatic	Metastatic
	Metastatic sites	Liver (87.6%)	Liver (85%)
		Lung (19.4%)	Lung (35%)
		Peritoneum (19.4%)	Peritoneum (4%)
	Tumor location	Head (39.2%)	Head (44%)
Response	ORR (%)	31.6	23
	PR (%)	31	23
	SD (%)	38.6	27
	DCR (%)	70.2	48
	PFS (mo)	6.4	5.5
	OS (mo)	11.1	8.5
	1-yr OS (%)	48.4	35
Safety (Grade 3-4 toxicities)	Neutropenia	45.7	38
	Febrile neutropenia	5.4	3
	Thrombocytopenia	9.1	13
	Anemia	7.8	13
	Fatigue	23.6	17
	Peripheral neuropathy	9	17
	Diarrhea	12.7	6
Side effects	Toxic death	0.6	4
	Alopecia	11.2	50
	G-CSF use	42.5	26

DCR: Disease control rate; GNP: Gemcitabine/nab-paclitaxel; PR: Partial response; ORR: Overall response rate; OS: Overall survival; SD: Stable disease.

Table 2 Comparison of the FOLFIRINOX and modified FOLFIRINOX trials

		ACCORD/PRODIGE trial (FOLFIRINOX)[9]	Stein et al[20] Modified FOLFIRINOX	Mahaseth et al[21] (Modified FOLFIRINOX)	Ghorani et al[22] (Modified FOLFIRINOX)
	Location	France	United States	United States	United Kingdom
	Number of patients	342	44	36	18
	Study design	Phase 2-3 Prospective	Phase 2 Prospective	Phase 2 Prospective	Retrospective
Study design	Dosing		25% reduction in bolus 5-FU and irinotecan doses	No 5-FU bolus	No 5-FU bolus and 25% reduction in irinotecan doses
Patient and tumor characteristics	Median age	61 years	62	63	60
	Sex distribution	Male (62%)	Male (56.8%)	Male (56.8%)	Male (44.6%)
	ECOG	PS 0 (37.4%)	PS 0 (46%)	PS 0 (22%)	PS 0 (56.6%)
		PS 1 (61.9%)	PS 1 (54%)	PS 1 (76%)	PS 1 (44.4%)
		PS 2 (0.6%)		PS 2 (1%)
	Tumor stage	Metastatic	Metastatic	Metastatic	Locally advanced and metastatic
	Metastatic sites	Liver (87.6%)	Liver (54.1%)
		Lung (19.4%)	Lung (32.4%)
		Peritoneum (19.4%)	Peritoneum (37.8%)
	Tumor location	Head (39.2%)	Head (54.8%)	NA	Head (566%)
Response	ORR (%)	31.6	35.1	30	47
	PR (%)	31	35.1	NA	47
	SD (%)	38.6	51.5	NA	23
	DCR (%)	70.2	86.6	NA	80
	PFS (mo)	6.4	6.1	8.5	7.2
	OS (mo)	11.1	10.2	9	9.3
	1-yr OS (%)	48.4	38	NA	NA
Safety (grade 3-4 toxicities)	Neutropenia	45.7	12.2	3	0
	Febrile N.	5.4	4.1	0	5.6
	Thrombocytopenia	9.1	9.5	4	0
	Anemia	7.8	5.4		0
	Fatigue	23.6	12.2	13	5.6
	Peripheral neuropathy	9	2.7	4	0
	Diarrhea	12.7	16.2	13	16.7
	Toxic death	0.6	0	0	0
Additional information			Pegfilgastrim on each cycle	Pegfilgastrim on each cycle	Pegfilgastrim on each cycle

DCR: Disease control rate; PR: Partial response; ORR: Overall response rate; OS: Overall survival; SD: Stable disease.

Table 3 Comparison of the gemcitabine/nab-paclitaxel and modified gemcitabine/nab-paclitaxel trials

		MPACT trial[10] (GNP)	Krishna et al[23] (Modified GNP)
Study design	Location	International	United States
	Number of patients	861	49
	Dosing		Omission of Day 7 doses
	Study design	Phase 3	Retrospective
Patient and tumor characteristics	Median age (yr)	62	65
	Sex distribution	Male (57%)	Male (57%)
	Tumor stage	Metastatic	Metastatic
	Metastatic sites	Liver (85%)	Liver (57%)
		Lung (35%)	Lung (27%)
		Peritoneum (4%)	Peritoneum (43%)
	Tumor Location	Head (44%)	Head (51%)
	PFS (mo)	5.5	4.8
	OS (mo)	8.5	11.1
Safety (Grade 3-4 toxicities)	Neutropenia	38	10
	Thrombocytopenia	13	4
	Anemia	13	15
	Fatigue	17	6
	Peripheral neuropathy	17	2
	Diarrhea	6	0

GNP: Gemcitabine/nab-paclitaxel; OS: Overall survival; PFS: Progression free survival.