Table Info

Table 2.

Phase II and III published study with immune checkpoint inhibitors in MBC, for which preliminary or final results have been presented and/or published

Trial	Design	Line of therapy	Population (n)	Drugs/ich test*	ORR% (95% CI)	Median PFS months (95% CI)	Median OS months (95% CI)	Ref.
KEYNOTE-086 (cohort B)	II	1	TNBC PD-L1+ (84)	Pembrolizumab	18 (13.9–31.4)	2.1 (2.0–2.2)	18 (12.9–23.0)	[44]
KEYNOTE-086 (cohort B)	II	1	TNBC PD-L1+ (84)	DAKO 22C3 pharmDx	18 (13.9–31.4)	2.1 (2.0–2.2)	18 (12.9–23.0)	[44]
KEYNOTE-086 (cohort A)	II	> 2	TNBC any PD-L1 (170)	Pembrolizumab	Total 5.3 (2.7–9.9)	Total 2 (1.9–2.0)	Total 9 (7.6–11.2)	[43]
KEYNOTE-086 (cohort A)	II	> 2	TNBC any PD-L1 (170)	DAKO 22C3 pharmDx	PD-L1+ 5.7 (2.4–12.2)	PD-L1+ 2 (1.9–2.1)	PD-L1+ 8.8 (7.1–11.2)	[43]
KEYNOTE-119	III	> 1	TNBC any PD-L1 (622)	Pembrolizumab (P) vs. CT^§	Total P: 2.1 (6.6–13.4)	Total P: 2.1 (2.0–2.1)	Total P: 9.9 (8.3–11.4)	[48]
				DAKO 22C3 pharmDx	CT: 3.3 (7.4–14.6)	CT: 3.3 (2.7–4.0)	CT: 10.8 (9.1–12.6)
					CPS ≥ 10 P: 17.7 (10.7–26.8) CT: 9.2 (4.3–16.7)	CPS ≥ 10 P: 2.1 (2.0–2.5) CT: 3.4 (2.3–4.1)	CPS ≥ 10 P: 12.7 (9.9–16.3) CT: 11.6 (8.3–13.7)
					CPS ≥ 1 P: 12.3 (8.1–17.6) CT: 9.4 (5.8–14.3)	CPS ≥ 1 P: 2.1 (2.0–2.1) CT: 3.1 (2.3–4.0)	CPS ≥ 1 P: 10.7 (9.3–12.5) CT: 10.2 (7.9–12.6)
IMpassion130	III	1	TNBC any PD-L1 (902)	Atezolizumab + NabP vs. NabP + placebo	Experimental arm PD-L1+ 58.9 (51.5–66.1)	Experimental arm PD-L1+ 7.5 (6.7–9.2)	Experimental arm PD-L1+ 25 (19.5–30.7)	[49]
				VENTANA SP142	Total 56.0 (51.3–60.6)	PD-L1-5.6 (5.5–7.3)	PD-L1-19.6 (16.3–21.6)
				VENTANA SP142	Control arm PD-L1+ 42.6 (35.4–50.1) Total 45.9 (41.2–50.6)	Control arm PD-L1+ 5.3 (3.8–5.6) PD-L1-5.6 (5.4–7.3)	Control arm PD-L1+ 18 (13.6–20.1) PD-L1-19.6 (16.9–22.2)
IMpassion131	III	1	TNBC any PD-L1 (651)	Atezolizumab + paclitaxel vs. paclitaxel + placebo	Experimental arm PD-L1+ 55 (45–65)	Experimental arm PD-L1+ 5.7 (5.4–7.2)	Experimental arm PD-L1+ 28.3 (19.1–NA)	[50]
				VENTANA SP142	ITT 47 (41–54)	ITT 5.6 (5.4–6.5)	ITT 22.8 (17.1–28.3)
				VENTANA SP142	Control arm ITT 63 (56–70)	Control arm ITT 6.0 (5.6–7.4)	Control arm ITT 22.1 (19.2–30.5)
KEYNOTE-355	III	1	TNBC any PD-L1 (847)	Pembrolizumab (P) + CT^§ vs. CT^§ + placebo	NA	ITT 7.5 (P + CT) 5.6 (CT)	NA	[51]
				DAKO 22C3 pharmDx		CPS ≥ 10 9.7 (P + CT) 5.6 (CT)
				DAKO 22C3 pharmDx		CPS ≥ 1 7.6 (P + CT) 5.6 (CT)
NCT03051659	II	≥ 2 lines of hormonal therapies and 0–2 lines of CT	HR+/HER2-	Eribulin mesylate (E) with or without pembrolizumab (P)	P + E: 25 E: 34	PD-L1+ P + E 4.1 (1.8–8.5) E 4.2 (2.8–5.9)	NA	[54]
				DAKO 22C3 pharmDx		TIL > 10% P + E 3.2 (0.4–NA) E 4.1 (2.3–NA)
						NLR > 4 P + E 5.2 (2.0–6.4) E 4.1 (2.1–4.6)
						TMB > 6 P + E 4.1 (2.1–5.8) 0 E 3.9 (1.6–6.2)
PANACEA	Ib/II	> 1 trastuzumab-based therapy	HER2+ trastuzumab-resistant (6 + 52) Any PD-L1	Pembrolizumab + trastuzumab	Phase II	Phase II	Phase II	[35]
PANACEA	Ib/II	> 1 trastuzumab-based therapy	HER2+ trastuzumab-resistant (6 + 52) Any PD-L1	DAKO 22C3 pharmDx	PD-L1+ 15 (7–29) PD-L1– 0 (0–18)	PD-L1+ 2.7 (2.6–4.0) PD-L1-2.5 (1.4–2.7)	PD-L1+ Not Reached PD-L1-7 (4.9–9.8)	[35]
KATE2	II	> 1 taxane and trastuzumab-based therapy or within 6 mounths of adjuvant therapy	HER2+ (133) Any PD-L1	Atezolizumab (A) + trastuzumab emtansine (T-DM1) vs. placebo (p) + T-DM1	Total A + T-DM1: 45 T-DM1 + p: 43	Total A + T-DM1: 8.2 T-DM1 + p: 6.8	NA	[36, 37]
				VENTANA SP142	PD-L1+ A + T-DM1: 54 T-DM1 + p: 33	PD-L1+ A + T-DM1: 8.5 T-DM1 + p: 4.1
				VENTANA SP142	PD-L1- A + T-DM1: 40 T-DM1 + p: 50	PD-L1- A + T-DM1: 6.8 T-DM1 + p: 8.2
TOPACIO	II	0–2	TNBC (55)	Niraparib + pembrolizumab	21 (12–33)	8.3 (2.1-NA)	NA	[63]
TOPACIO	II	0–2	TNBC (55)	DAKO 22C3 pharmDx	BRCA mutated 47 (24–70)	8.3 (2.1-NA)	NA	[63]
MEDIOLA	II	> 1	BRCA mutetd, HER2- (30)	Olaparib + durvalumab	Total 63.3 (43.9–80.1)	Total 8.2 (4.6–11.8)	Total 20.5 (16.2–23.9)	[62]
			TNBC (17)	VENTANA SP263	No prior lines 78 (40.0–97.2)	No prior lines 9.9 (2.2–13.8)	No prior lines 21.3 (9.0–NA)
					1 prior line 64 (30.8–89.1)	1 prior line 11.7 (1.9–NA)	1 prior line 22.7 (10.1–NA)
					2 prior lines 50 (18.7–81.3)	2 prior lines 6.5 (1.0–8.2)	2 prior lines 16.9 (4.6–NA)

ICH ASSAY: immunoistochemistry assay emplyed for PDL-1 status evaluation;

Chemotherapy according physician choice; NA: not available; CT: chemotherapy; CTX: cyclophosphamide; CDDP: cisplatin; ORR: overall response rate; HR: hormon receptor; CPS: PD-L1 combined positive score; TIL: tumor-infiltrating lymphocytes; NLR: neutrophil-lymphocyte ratio; PFS: progression free survival

Declarations

Author contributions

MVD, VG, NLV contributed conception and design of the review. FM and MSC wrote the first draft of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

VG reports grants (Institution) and personal fees from Roche, personal fees from Novartis, and personal fees from Eli Lilly, outside the submitted work. MVD reports personal fees from Genomic Health, EliLilly, and Celgene, outside the submitted work. NLV reports grants from EISAI; speaker bureau, travel expences for conference from ROCHE, GENTILI; advisory role from NOVARTIS and CELGENE; advisor role, travel expences for conference from PFIZER; advisory board from MSD, outside the submitted work. FM and MSC declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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