Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes

Abstract

The invention provides methods and compositions for treating locally advanced or metastatic breast cancer and for enhancing immune function in an individual having locally advanced or metastatic breast cancer. The methods comprise administering a PD-1 axis binding antagonist and a taxane.

1 - 164 . (canceled) 
     
     
         165 . A method for treating or delaying progression of locally advanced or metastatic triple-negative breast cancer (TNBC) in an individual comprising administering to the individual an effective amount of atezolizumab and nab-paclitaxel. 
     
     
         166 . The method of  claim 165 , wherein the atezolizumab is administered to the individual at a dose of about 800 mg to about 850 mg every two weeks. 
     
     
         167 . The method of  claim 166 , wherein the atezolizumab is administered to the individual at a dose of about 840 mg every two weeks. 
     
     
         168 . The method of  claim 165 , wherein the TNBC is metastatic TNBC. 
     
     
         169 . The method of  claim 165 , wherein the cancer cells in the individual express PD-L1. 
     
     
         170 . The method of  claim 165 , wherein:
 (i) the individual has had two or fewer prior cytotoxic treatment regimens for locally advanced or metastatic breast cancer;   (ii) the individual has never had prior targeted systemic treatment for locally advanced or metastatic breast cancer; or   (iii) the locally advanced or metastatic TNBC is unresectable.   
     
     
         171 . The method of  claim 165 , wherein the nab-paclitaxel is administered before the atezolizumab, simultaneous with the atezolizumab, or after the atezolizumab. 
     
     
         172 . The method of  claim 165 , wherein the nab-paclitaxel is administered to the individual at a dose of about 100 mg/m 2  to about 125 mg/m 2  every week. 
     
     
         173 . The method of  claim 172 , wherein the nab-paclitaxel is administered to the individual at a dose of about 100 mg/m 2  every week. 
     
     
         174 . The method of  claim 165 , wherein the atezolizumab and/or the nab-paclitaxel are administered intravenously. 
     
     
         175 . The method of  claim 165 , further comprising administering to the individual an effective amount of a chemotherapeutic agent. 
     
     
         176 . A method of enhancing immune function in an individual having locally advanced or metastatic TNBC comprising administering to the individual an effective amount of atezolizumab and nab-paclitaxel. 
     
     
         177 . The method of  claim 176 , wherein:
 (i) CD8+ T cells in the individual have enhanced priming, activation, proliferation, and/or cytolytic activity relative to prior to the administration of the atezolizumab and the nab-paclitaxel;   (ii) the number of CD8+ T cells is elevated relative to prior to administration of the atezolizumab and the nab-paclitaxel;   (iii) Treg function is suppressed relative to prior to the administration of the atezolizumab and the nab-paclitaxel; and/or   (iv) T cell exhaustion is decreased relative to prior to the administration of the atezolizumab and the nab-paclitaxel.   
     
     
         178 . The method of  claim 176 , wherein atezolizumab is administered to the individual at a dose of about 800 mg to about 850 mg every two weeks. 
     
     
         179 . The method of  claim 178 , wherein atezolizumab is administered to the individual at a dose of about 840 mg every two weeks. 
     
     
         180 . The method of  claim 176 , wherein the TNBC is metastatic TNBC. 
     
     
         181 . The method of  claim 176 , wherein the cancer cells in the individual express PD-L1. 
     
     
         182 . The method of  claim 176 , wherein:
 (i) the individual has had two or fewer prior cytotoxic treatment regimens for locally advanced or metastatic breast cancer;   (ii) the individual has never had prior targeted systemic treatment for locally advanced or metastatic breast cancer; or   (iii) the locally advanced or metastatic TNBC is unresectable.   
     
     
         183 . The method of  claim 176 , wherein the nab-paclitaxel is administered to the individual at a dose of about 100 mg/m 2  to about 125 mg/m 2  every week. 
     
     
         184 . The method of  claim 183 , wherein the nab-paclitaxel is administered to the individual at a dose of about 100 mg/m 2  every week. 
     
     
         185 . The method of  claim 176 , wherein the atezolizumab and/or the nab-paclitaxel are administered intravenously. 
     
     
         186 . The method of  claim 176 , further comprising administering to the individual an effective amount of a chemotherapeutic agent.