Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.
Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.
复制标题
DOI：
10.1038/s41523-021-00337-2
复制
发表时间：
2021-10-05
影响因子：
5.9
通讯作者：
Esserman LJ
中科院分区：
文献类型：
--
作者：
Yee D;Isaacs C;Wolf DM;Yau C;Haluska P;Giridhar KV;Forero-Torres A;Jo Chien A;Wallace AM;Pusztai L;Albain KS;Ellis ED;Beckwith H;Haley BB;Elias AD;Boughey JC;Kemmer K;Yung RL;Pohlmann PR;Tripathy D;Clark AS;Han HS;Nanda R;Khan QJ;Edmiston KK;Petricoin EF;Stringer-Reasor E;Falkson CI;Majure M;Mukhtar RA;Helsten TL;Moulder SL;Robinson PA;Wulfkuhle JD;Brown-Swigart L;Buxton M;Clennell JL;Paoloni M;Sanil A;Berry S;Asare SM;Wilson A;Hirst GL;Singhrao R;Asare AL;Matthews JB;Hylton NM;DeMichele A;Melisko M;Perlmutter J;Rugo HS;Fraser Symmans W;Van't Veer LJ;Berry DA;Esserman LJ
I-SPY2是一项适应性随机2期临床试验，评估新药与标准治疗紫杉醇、阿霉素和环磷酰胺联合治疗乳腺癌的新辅助治疗效果。Ganitumab是一种单克隆抗体，旨在结合并抑制I型胰岛素样生长因子受体（IGF-1R）的功能。Ganitumab与二甲双胍和紫杉醇（PGM）联合进行了测试，随后与单独的标准治疗进行了比较。虽然在激素受体阴性、her2阴性乳腺癌的PGM治疗组中，病理完全缓解（pCR）率在数值上更高（32%对21%），但这一小幅增长并未达到I-SPY预先设定的毕业门槛。尽管二甲双胍与ganitumab联合使用，PGM仍与高血糖和血红蛋白A1c升高相关。我们评估了几种推测的ganitumab反应的预测性生物标志物（例如，IGF-1配体评分、IGF-1R特征、IGFBP5表达、基线HbA1c）。虽然在两组中有几个特征与pCR相关，但没有一个是对PGM反应的特异性预测因子。抗igf - 1r治疗的任何进一步发展都需要更好地控制抗igf - 1r药物引起的高血糖，并开发更具预测性的生物标志物。
I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY’s prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.
登录
查看更多内容
影响因子：
--
作者：
Carrillo M;Rodriguez RM;Walsh CL;Mcgarvey M
通讯作者：
Mcgarvey M
DOI：
10.1158/1078-0432.ccr-13-3448
发表时间：
2014-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beltran PJ;Calzone FJ;Mitchell P;Chung YA;Cajulis E;Moody G;Belmontes B;Li CM;Vonderfecht S;Velculescu VE;Yang G;Qi J;Slamon DJ;Konecny GE
通讯作者：
Konecny GE
影响因子：
45.3
作者：
Jiralerspong, Sao;Palla, Shana L.;Gonzalez-Angulo, Ana M.
通讯作者：
Gonzalez-Angulo, Ana M.
影响因子：
158.5
作者：
Cardoso, F.;van't Veer, L. J.;Piccart, M.
通讯作者：
Piccart, M.
乳腺癌治疗veliparib-钙铂治疗的自适应随机化。
DOI：
10.1056/nejmoa1513749
发表时间：
2016-07-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Rugo HS;Olopade OI;DeMichele A;Yau C;van 't Veer LJ;Buxton MB;Hogarth M;Hylton NM;Paoloni M;Perlmutter J;Symmans WF;Yee D;Chien AJ;Wallace AM;Kaplan HG;Boughey JC;Haddad TC;Albain KS;Liu MC;Isaacs C;Khan QJ;Lang JE;Viscusi RK;Pusztai L;Moulder SL;Chui SY;Kemmer KA;Elias AD;Edmiston KK;Euhus DM;Haley BB;Nanda R;Northfelt DW;Tripathy D;Wood WC;Ewing C;Schwab R;Lyandres J;Davis SE;Hirst GL;Sanil A;Berry DA;Esserman LJ;I-SPY 2 Investigators
通讯作者：
I-SPY 2 Investigators