Abstract
Background: Previously we have shown that early development of rash is associated with a higher chance of achieving pathological complete response to neoadjuvant lapatinib. In the current analysis, we investigate its impact on survival in the ALTTO phase III adjuvant trial. Methods: In ALTTO, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomly assigned to adjuvant trastuzumab, lapatinib, their sequence, or their combination for a total duration of one year. We evaluated whether the development of early lapatinib-related rash (ie, within 6 weeks) is associated with disease-free (DFS) and overall survival (OS). Landmark analysis at eight weeks and time-dependent analysis were tested in a multivariable model stratifying on trial's stratification factors. All statistical tests were two-sided. Results: Out of 6098 lapatinib-treated patients, 3973(65.2%) were included in the landmark analysis, of whom 1389 (35.0%) had developed early rash. After median follow-up of 4.5 years, the development of early rash was associated with a trend of improved DFS (multivariable: hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.73 to 1.03, P =.10) and statistically significantly improved OS (multivariable: HR=0.63, 95% CI=0.48 to 0.82, P <.001) compared with subjects without early rash. Compared with patients randomly assigned to trastuzumab (n=2051), patients who were randomly assigned to trastuzumab/lapatinib combination and developed early rash (n=692) had superior DFS (multivariable: HR=0.72, 95% CI=0.55 to 0.92, P =.01) and OS (multivariable: HR=0.59, 95% CI=0.39 to 0.90, P =.01). Time-dependent analysis suggests that the occurrence of rash is predictive of lapatinib benefit, both when given in combination or sequential to trastuzumab. Conclusions: Our results indicate that early development of rash identifies patients who derive superior benefit from lapatinib-based therapy.
| Original language | English (US) |
|---|---|
| Article number | djw037 |
| Journal | Journal of the National Cancer Institute |
| Volume | 108 |
| Issue number | 8 |
| DOIs | |
| State | Published - 2016 |
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ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Cancer Research
Cite this
Lapatinib-related rash and breast cancer outcome in the ALTTO phase III randomized trial. / Sonnenblick, Amir; De Azambuja, Evandro; Agbor-Tarh, Dominique; Bradbury, Ian; Campbell, Christine; Huang, Yingjie; Dueck, Amylou; Pritchard, Kathleen I.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Perez, Edith A.; Piccart, Martine; Azim, Hatem A.
In: Journal of the National Cancer Institute, Vol. 108, No. 8, djw037, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lapatinib-related rash and breast cancer outcome in the ALTTO phase III randomized trial
AU - Sonnenblick, Amir
AU - De Azambuja, Evandro
AU - Agbor-Tarh, Dominique
AU - Bradbury, Ian
AU - Campbell, Christine
AU - Huang, Yingjie
AU - Dueck, Amylou
AU - Pritchard, Kathleen I.
AU - Wolff, Antonio C.
AU - Jackisch, Christian
AU - Lang, Istvan
AU - Untch, Michael
AU - Smith, Ian
AU - Boyle, Frances
AU - Xu, Binghe
AU - Gomez, Henry
AU - Perez, Edith A.
AU - Piccart, Martine
AU - Azim, Hatem A.
PY - 2016
Y1 - 2016
N2 - Background: Previously we have shown that early development of rash is associated with a higher chance of achieving pathological complete response to neoadjuvant lapatinib. In the current analysis, we investigate its impact on survival in the ALTTO phase III adjuvant trial. Methods: In ALTTO, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomly assigned to adjuvant trastuzumab, lapatinib, their sequence, or their combination for a total duration of one year. We evaluated whether the development of early lapatinib-related rash (ie, within 6 weeks) is associated with disease-free (DFS) and overall survival (OS). Landmark analysis at eight weeks and time-dependent analysis were tested in a multivariable model stratifying on trial's stratification factors. All statistical tests were two-sided. Results: Out of 6098 lapatinib-treated patients, 3973(65.2%) were included in the landmark analysis, of whom 1389 (35.0%) had developed early rash. After median follow-up of 4.5 years, the development of early rash was associated with a trend of improved DFS (multivariable: hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.73 to 1.03, P =.10) and statistically significantly improved OS (multivariable: HR=0.63, 95% CI=0.48 to 0.82, P <.001) compared with subjects without early rash. Compared with patients randomly assigned to trastuzumab (n=2051), patients who were randomly assigned to trastuzumab/lapatinib combination and developed early rash (n=692) had superior DFS (multivariable: HR=0.72, 95% CI=0.55 to 0.92, P =.01) and OS (multivariable: HR=0.59, 95% CI=0.39 to 0.90, P =.01). Time-dependent analysis suggests that the occurrence of rash is predictive of lapatinib benefit, both when given in combination or sequential to trastuzumab. Conclusions: Our results indicate that early development of rash identifies patients who derive superior benefit from lapatinib-based therapy.
AB - Background: Previously we have shown that early development of rash is associated with a higher chance of achieving pathological complete response to neoadjuvant lapatinib. In the current analysis, we investigate its impact on survival in the ALTTO phase III adjuvant trial. Methods: In ALTTO, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomly assigned to adjuvant trastuzumab, lapatinib, their sequence, or their combination for a total duration of one year. We evaluated whether the development of early lapatinib-related rash (ie, within 6 weeks) is associated with disease-free (DFS) and overall survival (OS). Landmark analysis at eight weeks and time-dependent analysis were tested in a multivariable model stratifying on trial's stratification factors. All statistical tests were two-sided. Results: Out of 6098 lapatinib-treated patients, 3973(65.2%) were included in the landmark analysis, of whom 1389 (35.0%) had developed early rash. After median follow-up of 4.5 years, the development of early rash was associated with a trend of improved DFS (multivariable: hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.73 to 1.03, P =.10) and statistically significantly improved OS (multivariable: HR=0.63, 95% CI=0.48 to 0.82, P <.001) compared with subjects without early rash. Compared with patients randomly assigned to trastuzumab (n=2051), patients who were randomly assigned to trastuzumab/lapatinib combination and developed early rash (n=692) had superior DFS (multivariable: HR=0.72, 95% CI=0.55 to 0.92, P =.01) and OS (multivariable: HR=0.59, 95% CI=0.39 to 0.90, P =.01). Time-dependent analysis suggests that the occurrence of rash is predictive of lapatinib benefit, both when given in combination or sequential to trastuzumab. Conclusions: Our results indicate that early development of rash identifies patients who derive superior benefit from lapatinib-based therapy.
UR - http://www.scopus.com/inward/record.url?scp=84992392061&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992392061&partnerID=8YFLogxK
U2 - 10.1093/jnci/djw037
DO - 10.1093/jnci/djw037
M3 - Article
C2 - 27098150
AN - SCOPUS:84992392061
VL - 108
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 8
M1 - djw037
ER -