PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review
Abstract
:1. Introduction
2. Anti-PD-1/PD-L1 Agents in Breast Cancer: Monotherapy
2.1. Pembrolizumab
2.2. Atezolizumab
2.3. Avelumab
3. Anti-PD-1/PD-L1 Agents in Breast Cancer: Combination with Chemotherapy
3.1. Advanced Cancers
3.1.1. Early Phase Studies
3.1.2. Randomized Studies
- -
- Weekly paclitaxel in the Impassion 131 study, which enrolled a similar patient population as in Impassion 130 and is under analysis.
- -
- Carboplatin-gemcitabine or capecitabine in the Impassion 132 study, which is dedicated to patients with an early relapse (<12 months) after anthracyclines/taxanes administered in the adjuvant/neoadjuvant setting and which is ongoing.
3.2. Early Settings
4. Anti-PD-1/PD-L1 in Breast Cancer: Combination with Targeted Therapies
4.1. Combination of Anti PD-1/PD-L1 Agents with PARP Inhibitors
4.1.1. Combination of PD-1/PD-L1 Inhibitors with Trastuzumab
4.1.2. Combination of PD-1/PD-L1 Inhibitors with CDK4/6 Inhibitors
4.1.3. Combination of PD-1/PD-L1 Inhibitors with MEK Inhibitors
5. Surrogate Markers of PD-1/PD-L1 Inhibitors Efficacy
6. Immune Combination Using PD(L)1 Inhibitors and Future Development in BC Immunotherapy
7. Conclusions
Supplementary Materials
Funding
Conflicts of Interest
References
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Ph. | Anti-PD(L)-1 | Single (S) or Combination | Study Title | Conditions or Disease | Treatment Line | Comparative Arm (for Phase IIR/III) | ORR (+/− 95% CI) | Duration of Response Median, Months (+/− 95% CI) | PFS Median, Months (+/− 95% CI) | OS Median, Months (+/− 95% CI) | Ref. |
---|---|---|---|---|---|---|---|---|---|---|---|
I | Atezolizumab | S | PCD4989g | M+ TNBC | ≥1 L | / | 1 L = 24% ≥2 L = 6% | 21 mo | 1.4 (1.3–1.6) | 17.6 mo (10.2–NR) | Emens JAMA Oncol 2019 |
Ib | Pembrolizumab | S | KEYNOTE-012 | M+ TNBC | ≥1 L | / | 18.5% | NA | 6-mo PFS rate = 24% | 12-mo OS rate = 43% | Nanda, BJC 2018 |
Ib | Pembrolizumab | S | KEYNOTE-028 | HR+ HER2− PDL1+ LA or M+ BC | ≥1 L | / | 12.0% (2.5–31) | 12.0 mo (7.4–15.9 mo). | NA | NA | Rugo, Clin Cancer Research 2018 |
Ib | Pembrolizumab | Chemotherapy (6 cohorts) | KEYNOTE-173 | LA TNBC | Neo-adj | / | Overall pCR = 60% (30–85) | NA | NA | NA | Schmid, SABCS 2018 |
Ib | Pembrolizumab | Abemaciclib | JPCE | HR+, HER2− M+ BC | 2 L/3 L | / | 14.3% | NA | NA | NA | Rugo SABCS 2017 Tolaney, ASCO 2018 |
Ib | Avelumab | S | JAVELIN | M+ BC | ≥1 L | / | Overall: 3% TNBC: 5.2% | NA | NA | NA | Breast Cancer Res Treat. 2018 |
Ib | Atezolizumab | Nab-paclitaxe | GP28328 | M+ TNBC | 1 L–3 L | / | 39.4% (22–57) | NA | 5.5 mo (5.1–7.7) | 14.7 mo (10.1–NR) | Adams JAMA Oncol 2018 |
Ib/II | Pembrolizumab | Trastuzumab | KEYNOTE-014 (PANACEA) | Trastuzumab resistant | / | PDL1+ = 15% PDL1− = | 3.5 mo (2.7–NR) | PDL1+:2.7 mo (2.6–4.0) PDL1−: 2.5 mo (1.4–2.7) | PDL1+: NR PDL1−: 7.0 mo (4.9–9.8) | Loi Lancet Oncol 2019 | |
II | Durvalumab | Olaparib | MEDIOLA | HER2-negative gBRCAm M+ BC | ≥1 L | / | 63% (44–80%) | 9.2 mo | 8.2 mo | NA | Domchek, SABCS 2018 |
II | Pembrolizumab | S | KEYNOTE-086 | M+ TNBC | ≥2 L | / | 5.3% (2.7–9.9) | NR | Median: 2.0 mo (1.9–2.0) | Median 9.0 mo (7.6–11.2) | Adams, Annals Oncol 2019 |
II | Pembrolizumab | Capecitabine | NCT03044730 | LA or M+ hormone-refractory or TNBC | ≥2 L | / | 14% | NA | Median: 4.1 mo (2.3–8.2) | Median 15.4 mo (8.2–16.6 mo) | Shah ASCO 2019 (#1096) |
II | Pembrolizumab | Paclitaxel or Capecitabine | NCT02734290 | LA or M+ TNBC | 1 L or 2 L | / | Cape = 43% Taxol = 25% | NA | NA | NA | Page ASCO 2019 (#1015) |
II | Pembrolizumab | Niraparib | TOPACIO | LA or M+ TNBC | 1 L to 5 L | / | 21% (12–33) | NA | Median: 2.5 mo (2.3–8.2) | NA | Vinayak, JAMA Oncol 2019 |
II | Pembrolizumab | S | TAPUR | M+ BC, high TMB (≥ 9 Muts/Mb) | ≥3 L | / | 21% (8–41) | NA | Median: 2.6 mo | Median: 7.9 mo | Alva ASCO 2019 (#1014) |
II | Atezolizumab | (Nab) paclitaxel + Cobimetinib | COLET | LA or M+ TNBC | 1 L | / | 34% | NA | 6-mo PFS rate: 40.5% | 6-mo OS rate: 84.1% | Brufski ASCO 2019 (#1013) |
II-R | Pembrolizumab | Standard Chemo | I-SPY 2 trial | LA TNBC | Neo-adj | Placebo | Pembro: 62% Placebo: 22% | NA | NA | NA | Nanda ASCO 2017 |
II-R | Pembrolizumab | Eribulin | KEYNOTE-150 (ENHANCE 1) (Study 218) | M+ TNBC | 1 L to 3 L | Eribulin +/− Pembrolizumab | 26.4% (2017) Equal in 2 arms (2019) | 8.3 mo (SABCS 2017) | P + E = 4.1 mo (ASCO 2019) E = 4.2 mo (ASCO 2019) | Median 17.7 (13.7–NR) (SABCS 2017) | Tolaney, SABCS 2017 Tolaney, ASCO 2019 (#1004) |
II-R | Nivolumab | Doxo or Cyclo or RT (3*8 Gy) | TONIC | M+ TNBC | 1 L to ≥3 L | Doxo or Cyclo or RT | Doxo = 35% Cyclo = 8% RT = 8% | NA | NA | NA | Voorwerk Nature Med 2019 |
II-R | Durvalumab | Nab-paclitaxel + standard EC | GeparNuevo | LA TNBC (cT2-cT4a-d) | Neo-adj | Placebo | pCR Durva: pCR placebo: 44% | NA | NA | NA | Loibl Annals Oncol 2019 |
III | Pembrolizumab | S | KEYNOTE-119 | M+ TNBC | 2 L or 3 L | single-agent CT (physician’s choice) | 4.8% | NA | NA | not superior to CT | Merck press release |
III | Atezolizumab | Nab-paclitaxel | IMPASSION-130 | LA or M+ TNBC | 1 L | Nab-paclitaxel | Atezo: 56% Placebo: 46% | HR= 0.78 (0.63–0.98) Median DOR Atezo: 7.4 mo Median DOR placebo: 5.6 | HR 0.62 (0.49–0.78) Median PFS Atezo: 7.2 mo Median PFS placebo: 5.5 mo | HR 0.86 (0.72–1.02 Median OS Atezo: 21.0 mo Median OS placebo: 18.7 mo | Schmid NEJM 2018 Schmid ASCO 2019 |
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Planes-Laine, G.; Rochigneux, P.; Bertucci, F.; Chrétien, A.-S.; Viens, P.; Sabatier, R.; Gonçalves, A. PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review. Cancers 2019, 11, 1033. https://doi.org/10.3390/cancers11071033
Planes-Laine G, Rochigneux P, Bertucci F, Chrétien A-S, Viens P, Sabatier R, Gonçalves A. PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review. Cancers. 2019; 11(7):1033. https://doi.org/10.3390/cancers11071033
Chicago/Turabian StylePlanes-Laine, Gabrielle, Philippe Rochigneux, François Bertucci, Anne-Sophie Chrétien, Patrice Viens, Renaud Sabatier, and Anthony Gonçalves. 2019. "PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review" Cancers 11, no. 7: 1033. https://doi.org/10.3390/cancers11071033
APA StylePlanes-Laine, G., Rochigneux, P., Bertucci, F., Chrétien, A. -S., Viens, P., Sabatier, R., & Gonçalves, A. (2019). PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review. Cancers, 11(7), 1033. https://doi.org/10.3390/cancers11071033