Table Info

Table 1.

Summary of clinical trials testing immune checkpoint inhibitors in early breast cancer (EBC), for which preliminary or final results have been presented and/or published

Trial	Design	Setting	Population (n)	Drugs (n per arm)	pCR rates % (95% CI)	OR (95% CI), P	Biomarker analysis	Ref.
GeparNuevo	II Randomized	Neoadjuvant	TN (174) Any PD-L1	Durvalumab (2w)^a → Durvalumab + NabP → Durvalumab + EC (88)	53.4 (42.5–61.4) Window cohort: 61.0	1.45 (0.80–2.63), P = 0.224	sTILs and PD-L1 (trend) associated with pCR, not predictive for Durvalumab benefit	[14]
				Durvalumab (2w)^a → placebo + NabP → placebo + EC (86)	44.2 (33.5–55.3) Window cohort: 41.4	Window cohort: 2.22 (1.06–4.64), P = 0.035	iTILs (increase between baseline and end of the window phase) predictive for Durvalumab benefit (OR 9.36, 95% CI 1.26–69.65, P = 0.029)
KEYNOTE-173	Ib	Neoadjuvant	TN (60) Any PD-L1	Pembrolizumab + 6 CT regimens (cohort A-F)^b	Overall: 60 (range: 49–71)	NA	sTILs and PD-L1 associated with pCR	[16]
KEYNOTE-522	III	Neoadjuvant	TN (602) Any PD-L1	Pembrolizumab + NabP-carboplatin → A/E-C + pembrolizumab (401)	64.8 (59.9–69.5)	Estimated treatment difference: 13.6% (5.4-21.8, P > 0.001)	PD-L1 associated with pCR, not predictive for Pembrolizumab benefit	[17]
KEYNOTE-522	III	Neoadjuvant	TN (602) Any PD-L1	Placebo + NabP-carboplatin → A/E-C + placebo (201)	51.2 (44.1–58.3)	Estimated treatment difference: 13.6% (5.4-21.8, P > 0.001)		[17]
NeoTRIPaPDL1	III	Neoadjuvant	TN (280) Any PD-L1	Atezolizumab + NabP-carboplatin (138)	43.5 (35.1–52.2)	1.11 (0.69–1.79), P = 0.66^c	PD-L1 associated with pCR, not predictive for Atezolizumab benefit	[19]
				NabP-carboplatin (142)	40.8 (32.7–49.4)
IMpassion031	III	Neoadjuvant	TN (333) Any PD-L1	Placebo + NabP → placebo + A (168)	41.1	Delta pCR 16.5 (5.9– 27.1), P = 0.0044^d	PD-L1 associated with pCR, not predictive for Atezolizumab benefit	[18]
				Atezolizumab + NabP → atezolizumab + A (165)	57.6
I-SPY 2	II Adaptive-randomized	Neoadjuvant	HER2- (205) Any PD-L1	Pembrolizumab + paclitaxel → AC (69)	Total: 44 (33–55) ^e TN: 60 (44–75) ^e HR+: 30 (17–43) ^e	Probability superior to control: Total: > 99.9% TN: > 99.9% HR+: 99.6%	NA	[15]
I-SPY 2	II Adaptive-randomized	Neoadjuvant	HER2- (205) Any PD-L1	Paclitaxel → AC (181)	Total: 17 (11–23) ^e TN: 22 (13–30) ^e HR+: 13 (7–19) ^e		NA	[15]
GIADA	II	Neoadjuvant	Luminal-B (43) Any PD-L1	EC → Nivolumab + triptorelin + exemestane	16.3 (7.4–34.9) ^f		TILs and specific immune infiltrate characteristics at baseline associated with pCR; anthracycline-induced increase in cytotoxic T-cells and decrease in T-regulatory T cells	[41]

window phase stopped after 117 patients recruited (ethical concerns);

CT regimens; cohort A: NabP → doxorubicin-cyclophosphamide (AC); cohort B: NabP-Carboplatin AUC6 → AC; cohort C: NabP-Carboplatin AUC5 → AC; cohort D: NabP-Carboplatin AUC2 → AC; cohort E: Paclitaxel-Carboplatin AUC5 → AC; cohort F: Paclitaxel-Carboplatin AUC2 → AC;

pCR was a secondary endpoint;

one-sided significance boundary P = 0.0184;

estimated rates of pCR;

2-step statistical design: second step (8 pCR/43 patients) not met;

w: weeks; NA: not available; pCR: pathologic complete response; OR: odds ratio; EC: epirubicin-cyclophosphamide; sTILs: stromal TILs; iTILs: intra-tumoral TILs; AC: doxorubicin-cyclophosphamide

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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