sharon sanders
Editor-in-Chief & President
PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial.
Chia SKL1, Martin M2, Holmes FA3, Ejlertsen B4, Delaloge S5, Moy B6, Iwata H7, von Minckwitz G8, Mansi J9, Barrios CH10, Gnant M11, Tomašević Z12, Denduluri N13, Šeparović R14, Kim SB15, Jakobsen EH16, Harvey V17, Robert N18, Smith J 2nd19, Harker G20, Zhang B21, Eli LD21, Ye Y21, Lalani AS21, Buyse M22, Chan A23.
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Neratinib's effect over placebo was significant in patients with PIK3CA-altered tumors (HR 0.41; 95% CI 0.17-0.90, P = 0.028) but not PIK3CA wild-type tumors (HR 0.72; 95% CI 0.36-1.41; P = 0.34). The interaction test was non-significant (P = 0.309).
CONCLUSIONS:
Although there was a greater absolute risk reduction associated with neratinib treatment of patients with PIK3CA-altered tumors in ExteNET, current data do not support PIK3CA alteration as a predictive biomarker of response to neratinib in HER2-positive EBC.
TRIAL REGISTRATION:
ClinicalTrials.gov , NCT00878709 . Trial registered April 9, 2009.
https://www.ncbi.nlm.nih.gov/pubmed/30867034
Patients who have PIK3CA wild type tumors in HER2+ tend to be hormone negative and are more likely to have achieved complete pathological response to chemotherapy treatments than those patients with PIK3CA altered tumors.
PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab.
Loibl S1, Majewski I2, Guarneri V3, Nekljudova V4, Holmes E5, Bria E6, Denkert C7, Schem C8, Sotiriou C9, Loi S10, Untch M11, Conte P3, Bernards R2, Piccart M9, von Minckwitz G4, Baselga J12.
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Overall, the pCR rate was significantly lower in the PIK3CA mutant compared with the wild-type group (16.2% versus 29.6%; P < 0.001). Within the hormone-receptor positive (HR+) subgroup, the PIK3CA mutant group had a pCR rate of only 7.6% compared with 24.2% in the wild-type group (P < 0.001).
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T/L tended to improve DFS compared with T in the wild-type cohort, especially in the HR- group [HR 0.72, 95% CI (0.41-1.25), P = 0.242].
CONCLUSION:
Overall PIK3CA mutant/HER2+ tumours had significantly lower pCR rates compared with wild-type tumours, however mainly confined to the HR+/PIK3CA mutant population. No definite conclusions can be drawn regarding survival.
https://www.ncbi.nlm.nih.gov/pubmed/27177864
Chia SKL1, Martin M2, Holmes FA3, Ejlertsen B4, Delaloge S5, Moy B6, Iwata H7, von Minckwitz G8, Mansi J9, Barrios CH10, Gnant M11, Tomašević Z12, Denduluri N13, Šeparović R14, Kim SB15, Jakobsen EH16, Harvey V17, Robert N18, Smith J 2nd19, Harker G20, Zhang B21, Eli LD21, Ye Y21, Lalani AS21, Buyse M22, Chan A23.
Author information
snip
Neratinib's effect over placebo was significant in patients with PIK3CA-altered tumors (HR 0.41; 95% CI 0.17-0.90, P = 0.028) but not PIK3CA wild-type tumors (HR 0.72; 95% CI 0.36-1.41; P = 0.34). The interaction test was non-significant (P = 0.309).
CONCLUSIONS:
Although there was a greater absolute risk reduction associated with neratinib treatment of patients with PIK3CA-altered tumors in ExteNET, current data do not support PIK3CA alteration as a predictive biomarker of response to neratinib in HER2-positive EBC.
TRIAL REGISTRATION:
ClinicalTrials.gov , NCT00878709 . Trial registered April 9, 2009.
https://www.ncbi.nlm.nih.gov/pubmed/30867034
Patients who have PIK3CA wild type tumors in HER2+ tend to be hormone negative and are more likely to have achieved complete pathological response to chemotherapy treatments than those patients with PIK3CA altered tumors.
PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab.
Loibl S1, Majewski I2, Guarneri V3, Nekljudova V4, Holmes E5, Bria E6, Denkert C7, Schem C8, Sotiriou C9, Loi S10, Untch M11, Conte P3, Bernards R2, Piccart M9, von Minckwitz G4, Baselga J12.
Author information
snip
Overall, the pCR rate was significantly lower in the PIK3CA mutant compared with the wild-type group (16.2% versus 29.6%; P < 0.001). Within the hormone-receptor positive (HR+) subgroup, the PIK3CA mutant group had a pCR rate of only 7.6% compared with 24.2% in the wild-type group (P < 0.001).
snip
T/L tended to improve DFS compared with T in the wild-type cohort, especially in the HR- group [HR 0.72, 95% CI (0.41-1.25), P = 0.242].
CONCLUSION:
Overall PIK3CA mutant/HER2+ tumours had significantly lower pCR rates compared with wild-type tumours, however mainly confined to the HR+/PIK3CA mutant population. No definite conclusions can be drawn regarding survival.
https://www.ncbi.nlm.nih.gov/pubmed/27177864