Table 1.
Select studies reporting on IMD incidence in patients receiving targeted therapy.
| Disease | References | Therapy | Study type | Patients (n) | IMD incidence with targeted therapy | Findings |
|---|---|---|---|---|---|---|
| Breast Cancer | Berghoff et al. (34) | Trastuzumab, lapatinib | Retrospective cohort | 201 | — | IMD incidence trended toward lower in trastuzumab (38.2%) vs. no trastuzumab (57.1%, p = 0.058). IMD incidence trended toward lower in lapatinib (30.8%) vs. no lapatinib (39.6%, p = 0.530). |
| Swain et al. (35) | Pertuzumab vs. placebo (each with trastuzumab + docetaxel) | RCT | 808 | — | IMD incidence trended toward higher in pertuzumab arm (13.7%) vs. placebo arm (12.6%). But, median time-to-CNS-metastasis greater in pertuzumab arm (15.0 months) vs. placebo arm (12.9 months; HR, 0.58; 95% CI 0.39–0.85; p = 0.0049). | |
| Viani et al. (29)* | Trastuzumab vs. no trastuzumab | Meta-analysis | 6,738 | Higher | IMD incidence higher in trastuzumab arms by 1.82-fold (95% CI 1.89–3.16; p = 0.009). | |
| Bria et al. (36)* | Trastuzumab vs. no trastuzumab | Meta-analysis | 6,738 | Higher | IMD incidence higher in trastuzumab arms (RR, 1.57; 95% CI 1.03–2.37; p = 0.033). | |
| Okines et al. (37) | Ado-trastuzumab emtansine | Retrospective cohort | 39 | — | IMD incidence 18% in patients receiving ado-trastuzumab emtansine, with median time-to-IMD 7.5 months (95% CI 3.8–9.6). No control. | |
| Musolino et al. (38) | Trastuzumab vs. no trastuzumab | Retrospective cohort | 1,429 | Higher | IMD incidence higher in patients receiving trastuzumab (10.5%) vs. no trastuzumab (2.9%). HER2+ status and trastuzumab, together, predictive for CNS events (HR, 4.3; 95% CI 1.5–11.8; p = 0.005). | |
| Yau et al. (39) | Trastuzumab | Retrospective cohort | 87 | — | IMD risk not observed to be higher than disease-free population (RR, 1.0; 95% CI 0.4–2.2; p = 0.09). No control. | |
| Melanoma | Sloot et al. (14) | BRAF/MEK inhibitor vs. chemo | Retrospective cohort | 610 | — | IMD incidence not higher in BRAF inhibitor vs. chemotherapy (OR, 1.3; 95% CI 0.6–2.49; p = 0.5129). |
| Peuvrel et al. (40) | Vemurafenib | Retrospective cohort | 86 | — | IMD incidence 20% in patients receiving vemurafenib, with median time-to-IMD 5.3 months (±4.3). No control. | |
| NSCLC | Heon et al. (31) | EGFR inhibitor | Retrospective cohort | 81 | Lower | IMD incidence lower in EGFR inhibitor arms (25% at 42 months) vs. historical comparators (40–55% at 35–37 months). No study control. |
| Wang et al. (28) | EGFR inhibitor vs. other therapy | Retrospective cohort | 1,254 | Higher | IMD incidence higher in EGFR inhibitor vs. other therapy (HR,1.36; 95% CI 1.14–1.64; p = 0.001). | |
| Su et al. (41) | Gefitinib vs.Erlotinib vs.afatinib | Retrospective cohort | 219 | — | IMD incidences at 24 months for gefitinib (13.9%), erlotinib (9.3%), and afatinib (28.3%) were not significantly different (p = 0.80). Hazard ratio for IMD in afatinib vs. gefitinib 0.49 (95% CI 0.34–0.71; p = 0.001) | |
| Fu et al. (42) | Bevacizumab + chemo vs. chemo | Retrospective cohort | 159 | Lower | IMD incidence at 24 months lower in the bevacizumab + chemo arm (14.0%) vs. chemo arm (31%, p <0.01). | |
| Ilhan-Mutlu et al. (43) | Bevacizumab vs. chemo | Retrospective cohort | 1,043 | Lower | IMD incidence at 24 months lower for bevacizumab (2.6%) vs. chemo (5.8%, p = 0.01; HR, 0.36; 95% CI 0.19–0.68; p = 0.001). | |
| Gadgeel et al. (18) | Crizotinib vs. alectinib | RCT | 181 | — | IMD incidence at 12 months lower for alectinib (4.6%; 95% CI 1.5–10.6%) vs. crizotinib (31.5%; 95% CI 22.1–41.3%). Time-to-CNS progression longer in alectinib vs. crizotinib (csHR, 0.14; 95% CI 0.06–0.33; p < 0.0001). | |
| Nishio et al. (44) | Crizotonib vs. alectinib | Retrospective cohort | 164 | — | Time-to-CNS progression longer in alectinib vs. crizotinib (HR, 0.19; 95% CI: 0.07–0.53; p = 0.0004). | |
| Zhao et al. (45) | Icotinib vs. chemo | Retrospective cohort | 396 | Lower | IMD incidence at 24 months lower for icotinib (10.2%) vs. chemotherapy (32.1%). Hazard ratio for IMD in chemotherapy vs. icotinib 3.32 (95% CI 1.89–5.82; p < 0.001). | |
| RCC | Verma et al. (46) | TKI vs. no TKI | Retrospective cohort | 338 | Lower | IMD incidence lower in TKI vs. no TKI (HR, 0.39; 95% CI 0.21–0.73; p = 0.003). |
| Dudek et al. (33) | TKI vs. no TKI | Retrospective cohort | 92 | Lower | IMD incidence lower in TKI vs. no TKI (per month incidence rate ratio 1.568; 95% CI 1.06–2.33). | |
| Massard et al. (47) | Sorafenib vs. placebo | Retrospective cohort | 139 | Lower | IMD incidence lower in sorafenib (3%) vs. placebo (12%, p < 0.05). | |
| Vanhuyse et al. (48) | Antiangiogenic** vs. other therapy | Retrospective cohort | 199 | — | IMD incidence in targeted therapy group (15.7%) lower than non-targeted therapy group (18.2%). However, targeted therapy was not associated with a lower cumulative rate of brain metastases (HR, 0.58; 95% CI 0.26–1.30; p = 0.18). | |
| HCC | Shao et al. (49) | Antiangiogenic therapy *** | Retrospective cohort | 158 | Higher | IMD incidence 7% in patients receiving antiangiogenic targeted therapies vs. 0.2–2.2% in historical comparators. Median time-to-IMD 9.6 months. |
- Incidence trends marked with a dash if study reports 1) insignificant results, 2) only comparison between multiple targeted therapies, or 3) no control.
*
Both Viani et al. and Bria et al. report on the same datasets.
**
Antiangiogenic therapies in Vanhuyse et al. study = sorafenib, sunitinib, bevacizumab, temsirolimus, or everolimus.
***
Antiangiogenic therapies in Shao et al. study = sorafenib, sorafenib plus tegafur/uracil, sunitinib, bevacizumab plus capecitabine, bevacizumab plus erlotinib, or thalidomide plus tegafur/uracil.
(cs)HR, (cause-specific) hazard ratio; RR, relative risk; RCT, randomized controlled trial; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; HCC, hepatocellular carcinoma; TKI, tyrosine kinase inhibitor (sorafenib or sunitinib); EGFR inhibitor, gefitinib or erlotinib; BRAF/MEK inhibitor, BRAF, vemurafenib or dabrafenib; MEK, cobimetinib or trametinib.