Skip to main content

Table 4 Efficacy and safety data from Eve prospective studies published after the BOLERO-2 trial in HR+, HER2− aBC/mBC

From: Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications

Everolimus
StudyStudy designPopulationN° of pts.Previous CT allowedMedian TD (mos)/(R)DIa (mg/d)ORRmPFS (mos)mOS (mos)Any grade AEs (%) (Eve combination)bG3/4 AEs (%) (Eve combination) bDiscontinuation ratec
4EVER [38], phase IIIb, open label, single armEve + Exe (10 + 25 mg/d)Postmenopausal HR+, HER2− LABC/mBC progressing on or after an NSAI (either adjuvant or for advanced disease)299bYes, any number of lines for LABC/mBC, prior Exe allowedTD/RDI, 4.4/0.988.9% (at 24 weeks)5.6mOS NR, OS at 48w 66.9%Overall 98.7%
Stomatitis 49.2%
Fatigue 36.1%
Diarrhea 26.4%
Nausea 26.1%
Overall 58.9%
Stomatitis 8.4%
GPHD 6.7%
Dyspnea 4.7%
Anemia 4.3%
24.7%
BRAWO [39], phase IV, non-interventionalEve + Exe (5–10 + 25 mg/d)HR+, HER2− LABC/mBC progressed after a NSAI Eve + Exe as per clinical practice2074Yes, previous Exe allowedTD 10 mg/d, 5.1
TD 5 mg/d, 4.6
8.2%6.6NAStomatitis 42.6%
Fatigue 19.8%
Stomatitis 3.9%
Fatigue 1.5%
26%
STEPAUT [40], phase IV, non-interventionalEve + Exe (5–10 + 25 mg/d)Postmenopausal HR+, HER2− LABC/mBC progressing on/after prior NSAIs in routine clinical practice225NSTD/DI, NA/NANA9.5NAStomatitis/mucositis 48%
Rash/exanthema 22.2%
Dyspnea/cough 22.2%
Stomatitis/mucositis 4.4%
GPHD/weight loss 2.7%
Inappetence /nausea 2.2%
NA
BALLET [41], phase IIIb, open label, single arm, expanded access trialEve + Exe (5–10 + 25 mg/d)Postmenopausal HR+, HER2− LABC/mBC progressing on/after prior NSAIs2133Yes, any number of lines for LABC/mBCTD/RDI, 3.7/0.98NANANAOverall 94.7%
Stomatitis 52.8%
Asthenia 22.8%
Diarrhea 16.8%
Rash 16.5%
Inappetence 16%
Overall 42.7%
Stomatitis 9.4%
Asthenia 3.6%
Hyperglycemia 2.9%
Dyspnea 2%
NIP 1.9%
17.1%
EVEREXES [42], phase IIIb, open label, single arm, Asia and AfricaEve + Exe (10 + 25 mg/d)Postmenopausal HR+, HER2− LABC/mBC progressing on/after prior NSAI (adjuvant or for LABC/mBC)232Yes, no more than 1 prior CT line for LABC/mBCTD/DI, NA/9.215.8%9.5NAStomatitis 60.4%
Skin toxicity 27.8%
Hyperglycemia 24.7%
Fatigue 17.2%
Weight loss 15.4%
Stomatitis 10.6%
Hyperglycemia 7%
Fatigue 2.2%
NIP 1.3%
Weight loss 0.9%
NA
BOLERO-4 [43], phase II, multicenter, open-label, single-armFirst line: Eve + Let (10 + 2.5 mg/d); at PD second line: Eve + Exe (10 + 25 mg/d)Postmenopausal HR+ HER2− LABC/mBC202, 50NoTD/DI, 14.8/8.5 and 2.9/8.345%, 6%22, 3.7mOS NR, OS at 24 m 78.7%Eve + Let
Overall 100%
Stomatitis 68.8%
Loss of weight 44%
Diarrhea 41%
Nausea 37%
Eve + Let
Overall 58%
Anemia 10% Hypertension 8%
Stomatitis 6%
Hypertriglyceridemia 6%
Eve + Let
15.8%
TAMRAD [44], phase II, open-label, randomizedEve + TAM (10 + 20 mg/d) vs. TAM (20 mg/d)Postmenopausal HR+, HER2−, LABC/mBC progressing on/after prior NSAI (adjuvant or for LABC/mBC)54, 57Yes, any number of lines for LABC/mBCTD/DI, 6.2/NA and 4.8/NA14%, 13%8.6, 4.5NR, 32.9Pain 82%
Fatigue 72%
Anemia 69%
Stomatitis 56%
Leukopenia 54%
Stomatitis 11%
Pain 9%
Infections 7%
Anorexia 7%
Fatigue 6%
Eve + TAM
22%
PrE0102 [45], phase II, randomized, double-blind, placebo-controlledEve + Fulve (10 mg/d)fvs. FulvePostmenopausal HR+ HER2− LABC/mBC
progressing on/after prior NSAI (adjuvant or for LABC/mBC)
66, 65Yes, no more than 1 prior CT line for LABC/mBCTD/DI, 5.1/NA and 4.6/NA18.2%, 12.3%10.3, 5.128.3, 31.4Mucositis 53%
Fatigue 42%
Rash 38%
Anemia 31%
Diarrhea 23%
Mucositis 11%
NIP 6%
Fatigue 6%
Eve + Fulv
20%
MANTA [46], phase II, open-label, randomizedEve + Fulve (10 mg/d)f, cVIS + Fulve, (50 mg BID)g, iVIS + Fulve (2 days on, 5 days off; 125 mg BID)h, FulvePostmenopausal HR+, LABC/mBC progressing on/after prior NSAI (either adjuvant or for LABC/mBC)65, 103, 98, 67Yes, no more than 1 prior CT line for LABC/mBCTD/DI, NA/NA for all arms41.2%, 30.4%, 28.6%, 25.0%12.3, 7.6, 8.0, 5.4NR, 27.1, 24.2, 24.4Stomatitis 60%
Asthenia 53.3%
Rash 50.0%
Diarrhea 31.7%
Decreased appetite 30.0%
Stomatitis 11.7%
Rash 5.0%
Asthenia 3.3%
Diarrhea 1.7%
Decreased appetite 1.7%
18.8%
Safra et al. [47], phase II, open-label, single-arm, multicenter trialEve + Let (10 + 2.5 mg/d)Postmenopausal ER+, HER2− LABC/mBC progressing on/after prior ET (either adjuvant or for LABC/mBC)72NoTD/DI, NA/NA23.3%8.822.9Fatigue 61.1%
Stomatitis 54.2%
Rash 33.4%
Cough 33.3%
Decreased appetite 31.9%
Anemia 9.7%
Stomatitis 8.3%
Fatigue 5.6%
Diarrhea 5.6%
Hyperglycemia 4.2%
12.5%
BOLERO-6 [48], phase II, open-label, randomizedEve + Exe (10 + 25 mg/d) vs. Eve (10 mg/d) vs. capecitabine (1250 mg/m2 BID)Postmenopausal HR+ HER2− LABC/mBC progressing on/after prior NSAI104, 103, 102Yes, no more than 1 prior CT line for LABC/mBC, prior Exe not allowedTD/RDI, 6.3/0.92, 4.6/0.98, and 6.1/0.78NA8.4, 6.8, 9.623.1, 29.3, 25.6Overall 100%
Stomatitis 49%
Fatigue 38%
Diarrhea 35%
Anemia 32%
GGT elevation 15%
AST elevation 15%
Overall 70%
Anemia 13%
Stomatitis 9%
GGT elevation 9%
Fatigue 8%
AST elevation 7%
Pneumonitis 7%
Eve + Exe
8%
Yardley et al. [49], phase II, open labelEve (10 mg/d) added to the most recent ET on which a patient progressedPost/premenopausal HR+, HER2− LABC/mBC refractory to ET (either adjuvant or for LABC/mBC)47Yes no more than 1 prior CT line for LABC/mBCTD/DI, 4.1/NA6%6.621.1Fatigue 38%
Stomatitis 32%
Mucosal
inflammation 28%
Rash 28%
Fatigue 4%
Stomatitis 6%
Mucosal inflammation 4%
Rash 4%
15%
  1. AEs adverse events, AST aspartate aminotransferase, BID bis in die, CT chemotherapy, cVIS continuous vistusertib, d day, Eve everolimus, Exe exemestane, ET endocrine therapy, Fulv fulvestrant, G grade, GGT gamma glutamyl transferase, GHPD general physical health deterioration, mos months, HER2 human epidermal growth factor receptor 2, HR hormone receptor, iVIS intermittent vistusertib, LABC locally advanced breast cancer, Let letrozole, mBC metastatic breast cancer, mg/d milligrams per day, mPFS median progression-free survival, mOS median overall survival, N° number, NA not available, NE not evaluable, NIP non-infectious pneumonitis, NR not reached, NS not specified, NSAI non-steroideal aromatase inhibitor, ORR overall response rate, PD progressive disease, pts. patients, (R)DI (relative) dose intensity, TAM tamoxifen, TD treatment duration, w weeks
  2. aOnly absolute but not relative dose intensity is calculated in mg/d
  3. bReported AEs refer only to the arm including Eve + ET
  4. cStudy treatment discontinuation (referring to the arm containing Eve + ET) due to AEs
  5. d281 patients evaluable for efficacy, 299 patients for safety
  6. eFulv 500 mg intramuscular injection on day 1, followed by 500 mg doses on days 15 and 28, and then every 28 days
  7. fRefers to Eve
  8. gRefers to cVIS
  9. hRefers to iVIS