Table 24Hierarchy of evidence, KQ4

Level of EvidenceStudynSettingTreatmentsOutcomeResults
RCT stratified on HER2 status/HER2-guided vs. non-HER2-guided
RCT prespecified MV SGA Gasparini 2007123MBC 1st, t+paclit vs. paclit+trastuzTTPCox regression sHER2 by treatment interaction p=.0538
ORRlogistic regression sHER2 by treatment interaction p=.6044
RCT post-hoc MV SGA
RCT treatment by HER2 SGACameron 2008367LABC/MBC 2nd, t+capecit (Cp)+/- lapatinib (Lp)PFScont sHER2/highest vs. other quartiles Cp p<.001, Cp+Lp0.12 Cp vs. Cp+Lp↑ highest quartile sHER2+ p<.001, other quartiles p=.002
Muller 2004101MBC 1st, t+/-epirub+paclit (ET) vs. epirub+cycloph (EC)OSET sHER2+↓ vs. - p=.092, EC sHER2+ vs. - p=NS
PFSsHER2- EC vs. ET p=NS, sHER2+ EC↓ vs. ET p=.0341
ORRET sHER2+ vs. - p=NS, EC sHER2+↓ vs. - p=.059
Lipton 2003562locally advanced, recurrent, MBC 1st, t?letrozole (LET) vs. tamoxifen (TAM)TTPsHER2+ LET↑ vs. TAM p=.0596, sHER2- LET↑ vs. TAM p=.0019
TTFsHER2+ LET↑ vs. TAM, p=.0418, sHER2- LET↑ vs. TAM p=.0066
ORRsHER2+ LET vs. TAM, p=.4507, sHER2- LET↑ vs. TAM p=.0078
CBsHER2+ LET vs. TAM, p=.3057, sHER2- LET↑ vs. TAM p=.0162
1-arm prespecified MV analysis Colomer 2007226MBC 2ndletrozole (LET)ORRunivariate sHER2+ ↓ vs. sHER2- p=.036
TTPunivariate sHER2+ ↓ vs. sHER2- p=.004
Cox regression sHER2+ ↓ vs. sHER2- p<.001
OSunivariate sHER2+ ↓ vs. sHER2- p<.0005
Colomer 200055MBC 1st, t+/-doxorub+paclitRDunivariate sHER2+↓ vs. sHER2- p=.035
RDCox regression sHER2+↓ vs. sHER2- p=.04
ORRunivariate sHER2+↓ vs. sHER2- p=.01
ORRlogistic regression sHER2↓ + vs. sHER2- p=.03
1-arm post-hoc MV analysis Yamauchi 199794MBC 1st, t?3 doses droloxifTTPCox regression sHER2+↓ vs. sHER2- p=.0003
OSCox regression sHER2+↓ vs. sHER2- p=.003
ORRunivariate sHER2+↓ vs. sHER2- p=.00001
ORRlogistic regression sHER2+↓ vs. sHER2- p=.0001
1-arm UV analysisIm 200538MBC 1st, t+/-epirub+paclitRDsHER2+↓ vs. sHER2- p=<0.001
TTPsHER2+↓ vs. sHER2- p=<0.001
OSsHER2+↓ vs. sHER2- p=<0.076
RespsHER2+ vs. sHER2- p=0.45
Fornier 200555MBC, t+/-paclit+trastuzORRsHER2+ vs. sHER2- p=1.0, sHER2 Δ<15 vs. Δ≥15 p=0.005
ORRsHER2 ≥15% vs. < 15% p=0.015
Esteva 200230MBC 2nd+, t+trastuz+docetORRsHER2+↑ vs. sHER2- p=0.04
Colomer 200442MBC 1st, t?paclit+gemcitabRDsHER2+↓ vs. sHER2- p=0.04
RespsHER2+↓ vs. sHER2- p=0.02
Luftner 200435MBC 2nd+, t?dose intense paclitRDsHER2+↓ vs. sHER2- p=0.042
PFSsHER2+↓ vs. sHER2- p=0.098
ORRsHER2+ vs. sHER2- p=0.40
Sandri 200439MBC 2nd+, t+/-cycloph+methotrexTTPsHER2+↓ vs. sHER2- p=0.007
OSsHER2+↓ vs. sHER2- p=<0.001
Burstein 200343MBC, t+trastuz+vinorelbProgrno ↓ in sHER2 predicted progression; baseline, Δ did not predict
Colomer 200647MBC 1st, t?IVvinorelb+IVgemcitORRsHER2+ vs. sHER2- p=0.9

Abbreviations: cycloph: cyclophosphamide; DFS: disease-free survival; droloxif: droloxifene; epirub: epirubicin; gemcit: gemcitabine; HR: hazard ratio; MV: multivariate; ORR: overall response rate; OS: overall survival; paclit: paclitaxel; pCR: pathologic complete response; PFS: progression-free survival; RCT: randomized, controlled trial; RD: residual disease; RFS: recurrence-free survival; SGA: subgroup analysis; TETR: time to early tumor recurrence; trastuz: trastuzumab; TTF: time to treatment failure; TTR: time to tumor recurrence; Tx: treatment; UV: univariate analysis; vinorelb: vinorelbine;

From: 3, Results and Conclusions

Cover of HER2 Testing to Manage Patients With Breast Cancer or Other Solid Tumors
HER2 Testing to Manage Patients With Breast Cancer or Other Solid Tumors.
Evidence Reports/Technology Assessments, No. 172.
Seidenfeld J, Samson DJ, Rothenberg BM, et al.

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