Table 5 Clinical trials co-targeting growth factor receptors in hormone-positive metastatic breast cancer patients
Study/phase | Patients | Prior hormone therapy experience | N | Regimen | Median PFS (months) | Grade ≥3 AEs |
|---|---|---|---|---|---|---|
EGFR inhibitors | ||||||
Phase II (Mayer et al. 2006) | ER/PgR-positive MBC | Hormone-sensitive population | 150 | Letrozole + erlotinib | Of 22 patients enrolled, 11/20 patients achieved clinical benefit (1 CR, 4 PR and 6 SD) | Hypermagnesemia, hypokalemia and scalp infection in 1 patient |
Phase II (Mita et al. 2005) | ER-positive MBC | Hormone-refractory population | 15 | Anastrozole + gefitinib | No clinical benefit | – |
Phase II (Cristofanilli et al. 2010) | ER/PgR-positive MBC | No prior endocrine therapy and/or developed metastatic disease during/after adjuvant tamoxifen | 93a | Anastrozole + gefitinib | 14.7 | Diarrhea 7 vs. 0 % Fatigue 5 vs. 4 % Hot flash 2 vs. 0 % |
Anastrozole + placebo | 8.4 | |||||
Phase II (Osborne et al. 2011) | ER/PgR-positive MBC | Patients with newly metastatic disease or recurring after adjuvant tamoxifen | 206b | Tamoxifen + gefitinib | 10.9 | Diarrhea 4 vs. 0 % Rash 4 vs. 0 % Vomiting 2 vs. 2 % |
Tamoxifen + placebo | 8.8 | |||||
ER/PgR/HER2-positive MBC | 37 | Tamoxifen + gefitinib | 6.7 | – | ||
Tamoxifen + placebo | 5.8 | |||||
TAnDEM/phase III (Kaufman et al. 2009) | ER/PgR/HER2-positive MBC | Previous treatment with tamoxifen as adjuvant or hormonal therapy for MBC or anastrozole was permitted (begun up to 4 weeks before random assignment) | 207 | Anastrozole + trastuzumab | 4.8 (independent assessment) | Vomiting 3 vs. 1 % Hypertension 2 vs. 4 % |
Anastrozole | 2.4 (independent assessment) | |||||
EGF30008/phase III(Johnston et al. 2009) | ER/PgR/HER2-positive MBCc | No prior therapy for advanced or metastatic disease was allowed. Prior neoadjuvant/adjuvant antiestrogen/adjuvant aromatase inhibitor and/or trastuzumab, (completed >1 year before study entry) | 219 | Letrozole + lapatinib | 8.2 | Diarrhea 10 vs. <1 % Rash 1 vs. 0 % |
Letrozole + placebo | 3.0 | |||||
ER/PgR-positive HER2-negative MBC (relapsed <6 months after stopping adjuvant tamoxifen) | 200 | Letrozole + lapatinib | 8.3 | – | ||
Letrozole + placebo | 3.1 | |||||
ER/PgR-positive HER2-negative MBC with low ER expression (ER H-score <160) (Finn et al. 2009) | 207 | Letrozole + lapatinib | 13.6 | |||
Letrozole + placebo | 6.6 | |||||
eLEcTRA/phase III(Huober et al. 2012) | ER/PgR/HER2-positive MBC | First-line treatment; no prior hormone therapy | 26 | Letrozole + trastuzumab | 14.1 | Bone pain 4 vs. 7 % Dyspnea 0 vs. 7 % |
31 | Letrozole | 3.3 | ||||
ER/PgR-positive HER2-negative MBC | 35 | Letrozole | 15.2 | Bone pain 6 % | ||
mTOR inhibitors | ||||||
TAMRAD (Bachelot et al. 2012) | ER/PgR-positive HER2-negative MBC | Aromatase inhibitor-resistant | 111 | Tamoxifen + everolimus | Clinical benefit rate = 61 % | Stomatitis 11 vs. 0 % Pain 9 vs. 18 % Infection 7 vs. 5 % Anorexia 7 vs. 4 % |
Tamoxifen | Clinical benefit rate = 42 % | |||||
BOLER0-2/phase III (Baselga et al. 2012) | ER/PgR-positive advanced breast cancer | Aromatase inhibitor-resistant | 724 | Exemestane + everolimus | 6.9 | Stomatitis 8 vs. 1 % Anemia 6 vs. <1 % Dyspnea 4 vs. 1 % Hyperglycemia 4 vs. 1 % Fatigue 4 vs. 1 % Pneumonitis 3 vs. 0 % |
Exemestane + placebo | 2.8 | |||||