Table 4 Effect of Treatment Mechanisms of Action on Survival, Tumor Response, Time to Progression
Citation | Therapy After BM | Outcome Assessed |
|---|---|---|
HER2-targeted monoclonal antibodies | ||
Ahn et al., 2013 [17] | Trastuzumab | OS after diagnosis of distant metastasis: trastuzumab, 26.9 mo; no trastuzumab, 19.1 mo; P = 0.020 |
Berghoff et al., 2012 [30] | Trastuzumab | OS after BM diagnosis, 7 mo (95% CI, 4.3–969); trastuzumab-based therapy after completion of local therapy for BM (surgery, radiotherapy), 14 mo (95% CI, 7.22–20.78); vs. not, 4 mo (95% CI, 2.40–5.61) |
Brufsky et al., 2011 [31] | Trastuzumab | OS after BM diagnosis, 13.0 mo (range, 0.1–55.5); trastuzumaba, 17.5 mo; vs. no trastuzumab, 3.7 mo; adjusted hazard ratio = 0.33 (95% CI, 0.25–0.46) |
Niwinska et al., 2010 [39] | Trastuzumab | OS after BM diagnosis ▪ HER2+/HR+: trastuzumab + chemotherapy after WBRT, 13 mo; chemotherapy alone after WBRT, 8 mo; no systemic treatment after WBRT, 2 mo; P < 0.001 ▪ HER2+/HR-: trastuzumab + chemotherapy after WBRT, 10 mo; chemotherapy alone after WBRT, 8 mo; no systemic treatment after WBRT, 4 mo; P = 0.004 |
Bergen et al., 2021 [19] | Trastuzumab + Pertuzumab | OS after BM diagnosis, trastuzumab + pertuzumab, 44 mo; other HER2-targeted therapy, 17 mo; no HER2-targeted therapy, 3 mo (P < 0.001) Overall intracranial CBR, trastuzumab + pertuzumab as systemic first-line therapy after diagnosis of BM, 100% Overall intracranial ORR, trastuzumab + pertuzumab as systemic first-line therapy after diagnosis of BM, 92.9% |
HER2-targeted non-monoclonal antibodies | ||
Anwar et al., 2021 [32] | Pyrotinib | OS after pyrotinib initiation, pyrotinib + surgery/radiation, 20.7 mo; pyrotinib only, 12.4 mo (P = 0.021) PFS after pyrotinib initiation, pyrotinib + surgery/radiation, 10.0 mo; pyrotinib only, 7.7 mo (P = 0.19) CBR after pyrotinib initiation, pyrotinib + surgery/radiation, 58.6%; pyrotinib only, 41.4% ORR after pyrotinib initiation pyrotinib + surgery/radiation, 24.1%; pyrotinib only, 31.0% |
HER2-targeted monoclonal antibodies + Tyrosine kinase inhibitors | ||
Braccini et al., 2013 [36] | Trastuzumab + Lapatinib | OS after BM diagnosis, trastuzumab and lapatinib (sequential), 25.7 mo (95% CI, 17.1–33.3); only 1 of the 2 targeted therapies, 9.6 mo (95% CI, 8.2–12.8); P < 0.001 |
Kaplan et al., 2012 [33] | Trastuzumab + Lapatinib | OS after BM diagnosis, trastuzumab- and lapatinib-based therapy (sequential), 23.6 mo; only 1 of the 2 targeted therapies, 14.6 mo; P = 0.023 |
Hayashi et al., 2015 [25] | Trastuzumab + Lapatinib | OS after BM diagnosis, trastuzumab and lapatinib had a longer survivalb than trastuzumab alone, lapatinib alone, or no HER2-targeting agent; P < 0.001 |
Tyrosine kinase inhibitors + other anti-HER2 therapies (not otherwise specified) | ||
Morikawa et al., 2018 [27] | Anti-HER2 therapy + Lapatinib | OS from BM diagnosis, 19.4 mo (95% CI, 15.5–26.6); anti-HER2 therapy with lapatinib vs. no use, adjusted hazard ratio = 0.26 (95% CI, 0.13–0.52); anti-HER2 therapy without lapatinib vs. no use, adjusted hazard ratio = 0.32 (95% CI, 0.18–0.59) |
Anti-HER2 therapies (not otherwise specified) | ||
Braccini et al., 2013 [36] | Anti-HER2 therapy | ▪ OS after BM diagnosis, 11.9 mo (95% CI, 8.7–15.5); anti-HER2 therapy, 15.2 mo (95% CI, 11.5–19.4); without anti-HER2 therapy, 3.4 mo (95% CI, 1.4–6) ▪ Cerebral progression-free survival, anti-HER2 therapy, 6.3 mo (95% CI, 7.8–11.5); without anti-HER2 therapy, 5.5 mo (95% CI, 1.2–6.7) |
Kaplan et al., 2012 [33] | HER2-targeted therapy (includes all patients receiving trastuzumab, lapatinib, or both) | OS after BM diagnosis; HER2-targeted therapy, 16.7 mo; without HER2-targeted therapy, 4.7 mo; P < 0.001 |
Gori et al., 2019 [24] | Anti-HER2 therapy | OS after BM diagnosis, 24.5 mo; HER2-targeted therapy (27.5 mo) vs. without anti-HER2 therapy (13.8 mo) (hazard ratio = 0.44 [95% CI, 0.25–0.78]) vs. no systemic therapy (2.1 mo) (hazard ratio = 0.09 [95% CI, 0.05–0.16]) |
Maurer et al., 2018 [26] | Anti-HER2 treatment | No impact on the development of a second CNS event or on OS. OS, 20.8 mo (IQR, 5.36-not reached) |
Mounsey et al., 2018 [20] | HER2-targeted therapy (includes trastuzumab, lapatinib, pertuzumab, and T-DM1) | ▪ Mortality after BM, receipt of HER2-targeted therapy after BM diagnosis, adjusted hazard ratio = 0.61 (95% CI, 0.39–0.97) ▪ OS after BM diagnosis, 18.1 mo (95% CI, 14.9–24.6); HER2-targed therapy (62% of patients), 25.3 mo (95% CI, 18.6–31.2); without HER2-targeted therapy, 7.8 mo (95% CI, 4.56–15.0) |
Yap et al., 2012 [18] | Anti-HER2 therapy (includes trastuzumab alone, lapatinib alone, or trastuzumab and lapatinib combined) | OS after BM diagnosis, 10.9 mo (95% CI, 9.0–11.9); anti-HER2 therapy, 18.5 mo; no anti-HER2 therapy, 5.7 mo; adjusted hazard ratio = 0.62 (95% CI, 0.43–0.89) |
Zhang et al., 2016 [28] | Anti-HER2 therapy (includes trastuzumab alone, lapatinib alone, or trastuzumab and lapatinib combined) | OS after BM diagnosis, 12 mo (range, 1–94); anti-HER2 therapy after WBRT, 21 mo, no anti-HER2 therapy after WBRT, 9 mo; P = 0.002 |
Bergen et al., 2021 [19] | HER2-targeted therapy, or no HER2-targeted therapy | OS after BM diagnosis, other HER2-targeted therapy, 17 mo; no HER2-targeted therapy, 3 mo |