CALGB-9433

Henderson IC, JCO, 2003

ResectedN+ early-BC

Followed by ACR

Paclitaxel

No further chemotherapy

5-yr DFS: 70%5-yr OS: 80%

5-yr DFS: 65%5-yr OS: 77%

HR for DFS: 0.83, HR for OS: 0.82, in favor of Paclitaxel

Adjuvant paclitaxel improves both DFS and OS in N+ breast cancer patients.

Cochrane MA on neoadjuvant chemotherapy in early-BC

Mieog JS, Cochrane Syst Rev, 2007

Neoadjuvant vs Adjuvant CT trials for early-stage BC

pCR after neoadjuvant CT

No-pCR after neoadjuvant CT

OS (OR: 0.48)DFS (OR: 0.48)In favor of pCR

pCR: pathologic complete responseOS analysis (4 trials, 1290 pts)DFS analysis (5 trials, 1741 pts)

Achieving pCR after neoadjuvant CT nearly doubles both OS and DFS

NSABP-B27

Rastogi P, JCO, 2008

Early-stage BC(n=2412) R

Pre-operative AC + Docetaxel

Pre-operative AC

pCR: 13%

pCR: 26%

No difference in OS/DFSp<0.001

Neoadjuvant docetaxel added to anthracyclines doubles pCR rate in early-stage BC patients

Phase 3 trialBC: Breast cancerAC: Doxorubicin + CyclophosphamidepCR: Pathologic complete response

pCR after neoadjuvant chemotherapy (NACT) in different BC sub-groups

Houssami N, Eur J Cancer, 2012

Triple-negative (HR-, Her2-) and Her2+ (HR-) patients achieve higher pCR after neoadjuvant chemotherapy.

Meta-analysisNACT: Neoadjuvant chemotherapypCR: pathologic complete responseBC: Breast cancerHR+: Hormone-receptor positive

Early-stage BC patients undergoing

NACT

pCR rate

HR+ / Her2-: 8.3%

HR+ / Her2+: 18.7%

HR- / Her2+: 38.9%

HR- / Her2-: 31.1%

If treated with anti-Her2 agents

NeoSphere

Gianni L, Lancet Oncol, 2012

Early-stage Her2+ BC

(421 pts)R

Pre-operative Trastuzumab +

Docetaxel + Pertuzumab

Pre-operative Trastuzumab +

Docetaxel

pCR: 45%

pCR: 29%

Phase 2 trialpCR: Pathologic complete responseOther arms not showed (Docetaxel + Pertuzumab, Trastuzumab + Pertuzumab)

Neoadjuvant dual Her2 block with trastuzumab and pertuzumab plus chemotherapy significantly increases pathologic complete response in operable Her2+ BC patients

GeparSixto

von Minckiwits G, Lancet Oncol, 2014

Early-stage BC(n=296) R

TNBC: Pre-Opertative CT with

Carboplatin

TNBC:Pre-operative CT without Carboplatin

pCR: 53%

pCR:36%

Phase 2 trialTNBC: Triple negative breast cancerpCR: Pathologic complete responseOther arms not showed (Her2+, HR+, etc; no benefit of carboplatin in these groups).

Neoadjuvant carboplatin (in addition to anthracyclines and taxanes) improves pathologic complete response in early-stage triple negative breast cancer patients.

CALGB 40603 (ALLIANCE)

Golsahm M, Ann Surg, 2015

Early-stage BCBCT-ineligible

Neo-adjuvant CT(n=185)

BCT-eligible

BCT-ineligible

78 (42%)

107 (58%)

Phase 2 trial, 2x2 factorial designBCT: Breast-conserving therapyOther arms not showed (ie, BCT-eligible at enrollment).

Neoadjuvant chemotherapy achieves breast-conservation elegibility in 42% of initially BCT-ineligible breast cancer patients

Create-X

Toi M, SABCS, 2015

Non-pCR after resection early-stage HR+ BC

patients treated with neoadjuvant CT

(n=900)

R

Capecitabine + Hormone-Therapy

Hormone-Therapy(no further CT)

5-yr DFS: 74%5-yr OS: 89%

5-yr DFS: 68%5-yr OS: 84%

Phase 3 trialpCR: complete response.HR+: Hormone receptor positiveCT: ChemotherapyDFS: Disease-free survivalOS: Overal survival

Adjuvant capecitabine (+ hormonal therapy) improves both DFS and OS in non-pCR after neoadjuvnt CT in HR+ BC patients

HR for DFS: 0.7 in favor of CapecitabineHR for OS: 0.6 in favor of Capecitabine