Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer

Figures & data

Table 1 Trials Evaluating the Use of Immune Checkpoint Inhibitor in Combination with Radiotherapy, Molecular Therapies or Chemotherapy That Reported the Preliminary Results in Metastatic Breast Cancer

NCT Number	Immune Checkpoint Inhibitor	Combination Therapy	Phase	Number of Enrolled Patients	Enrolled Patients	Key Results
Radiotherapy
NCT2730130	Pembrolizumab	Radiotherapy	Phase 1	17	Metastatic TNBC	Three of nine evaluable patients (33%) had PRs. One patient (11%) had SD.
_	Tremelimumab	Local radiation	Phase 1	6	Locally recurrent or metastatic BC	One SD was achieved as the best response. Tremelimumab at 3mg/kg combined with radiation therapy was well-tolerated.
Chemotherapy
NCT1633970	Atezolizumab	Nab-paclitaxel	Phase 1b	33	Metastatic TNBC	The ORR was 39.4% (95% CI, 22.9–57.9%), including 1 CR and 12 PRs. The DCR was 51.5% (95% CI, 33.5–69.2%).
NCT2425891	Atezolizumab	Nab-paclitaxel	Phase 3	902	Untreated metastatic TNBC	Median PFS were 7.2 months (95% CI 5.6–7.5) and median OS was 21.3 months (95% CI 17.3–23.4) for all patients. Median OS for PD-L1+ patients was 25.0 months(95% CI 22.6-not established)
NCT2513472	Pembrolizumab	Eribulin mesylate	Phase 1/2	106	Metastatic TNBC	For the 49 PD-L1-positive patients, the ORR was 30.6%. For patients with PD-L1-negative (n=49), the ORR was 22.4%.
HER-2-targeted therapy
NCT2129556	Pembrolizumab	Trastuzumab	Phase 1b/2	Phase1b:6 phase 2:52	PD-L1+, trastuzumab-R, advanced, HER2+BC	Phase 1b trial, there is no dose-limiting toxicities. Phase 2 trial, six (15%, 90% CI 7–29) of 40 PD-L1+ patients achieved an OR. There were no objective responders among the PD-L1- patients.
NCT2924883	Atezolizumab	T-DM1	Phase 2	202	Previously treated HER2+ MBC	Among ITT population: no statistically significant difference in PFS between combination therapy and single-agent TDM1. In the ITT population, 1-year OS was 89% in both groups. In the PD-L1+ subgroup, 1-year survival rate was 94% for combination group vs 88% for TDM1.
NCT2649686	Durvalumab	Trastuzumab	Phase 1	14	Heavily pretreated HER2+ MBC	No responses were observed, only with 29% patients showing stable disease at week 6.
PARP inhibitors
NCT2734004	Durvalumab	Olaparib	Phase 1/2	34	BRCA1/2-mutated and HER2- MBC	The DCR at 12 weeks was 24/30 (80%). The DCR at 28 weeks was 15/30 (50%). 19 confirmed responses were observed. This combination was well-tolerated with safety.
NCT2657889	Pembrolizumab	Niraparib	Phase 2	47	mTNBC	The ORR was 21%, including 5 CRs, 5 confirmed PRs, 13 SDs.
CDK4/6 inhibitors
NCT2079636	Pembrolizumab	Abemaciclib	Phase 1	28	ER+, HER2-MBC	Four patients (14%) showed an objective response at 24 weeks.
Dual checkpoint blockade therapy
NCT2536794	Durvalumab	Tremelimumab	Phase 2	18	Metastatic ER+ BC and TNBC	3 responses were achieved and only observed in patients with TNBC

Abbreviations: NCT, clinicalTrials.gov registry number; CI, confidence interval; Nab-paclitaxel, nanoparticle albumin-bound paclitaxel; PARP, poly (ADP-ribose) polymerase; T-DM1, trastuzumab emtansine; trastuzumab-R, trastuzumab-resistant; PD-L1, programmed death ligand-1; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer; mTNBC, metastatic triple-negative breast cancer; MBC, metastatic breast cancer; BC, breast cancer; DCR, disease control rate; ORR, overall response rate; OR, objective response; CR, complete response; PR, partial response; SD, stable disease; PFS, progression-free survival; OS, overall survival; ITT, Intention to treat; BRCA, breast cancer gene.