***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose Abemaciclib , a cyclin-dependent kinase 4 and 6 inhibitor , demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive , human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy . Methods MONARCH 3 is a double-blind , r and omized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive , HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting . Patients received abemaciclib or placebo ( 150 mg twice daily continuous schedule ) plus either 1 mg anastrozole or 2.5 mg letrozole , daily . The primary objective was investigator-assessed progression-free survival . Secondary objectives included response evaluation and safety . A planned interim analysis occurred after 189 events . Results Median progression-free survival was significantly prolonged in the abemaciclib arm ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.72 ; P = .000021 ; median : not reached in the abemaciclib arm , 14.7 months in the placebo arm ) . In patients with measurable disease , the objective response rate was 59 % in the abemaciclib arm and 44 % in the placebo arm ( P = .004 ) . In the abemaciclib arm , diarrhea was the most frequent adverse effect ( 81.3 % ) but was mainly grade 1 ( 44.6 % ) . Comparing abemaciclib and placebo , the most frequent grade 3 or 4 adverse events were neutropenia ( 21.1 % v 1.2 % ) , diarrhea ( 9.5 % v 1.2 % ) , and leukopenia ( 7.6 % v 0.6 % ) . Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy , significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive , HER2-negative advanced breast cancer PURPOSE To compare the efficacy and tolerability of tamoxifen with that of letrozole , an oral aromatase inhibitor , with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer . PATIENTS AND METHODS Nine hundred seven patients were r and omly assigned  letrozole 2.5 mg once daily ( 453 patients ) or tamoxifen 20 mg once daily ( 454 patients ) . Patients had estrogen receptor- and /or progesterone receptor-positive tumors , or both receptors were unknown . Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment . One prior chemotherapy regimen for metastatic disease was allowed . The primary end point was time to progression ( TTP ) . Secondary end points included overall objective response rate ( ORR ) , its duration , rate and duration of clinical benefit , time to treatment failure ( TTF ) , overall survival , and tolerability . RESULTS TTP was significantly longer for letrozole than for tamoxifen ( median , 41 v 26 weeks ) . Treatment with letrozole reduced the risk of progression by 30 % ( hazards ratio , 0.70 ; 95 % confidence interval , 0.60 to 0.82 , P = .0001 ) . TTP was significantly longer for letrozole irrespective of dominant site of disease , receptor status , or prior adjuvant antiestrogen therapy . Similarly , TTF was significantly longer for letrozole ( median , 40 v 25 weeks ) . ORR was higher for letrozole ( 30 % v 20 % ; P = .0006 ) , as was the rate of clinical benefit ( 49 % v 38 % ; P = .001 ) . Survival data are currently immature and not reported here . Both treatments were well tolerated . CONCLUSION Letrozole was significantly superior to tamoxifen in TTP , TTF , ORR , and clinical benefit rate . Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer PURPOSE The efficacy and tolerability of anastrozole ( Arimidex ; AstraZeneca , Wilmington , DE , and Macclesfield , United Kingdom ) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women . PATIENTS AND METHODS The r and omized , double-blind , multicenter study was design ed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor-positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy . Primary end points were objective response ( OR ) , defined as complete ( CR ) or partial ( PR ) response , time to progression ( TTP ) , and tolerability . RESULTS Anastrozole was as effective as tamoxifen in terms of OR ( 21 % v 17 % of patients , respectively ) , with clinical benefit ( CR + PR + stabilization > or = 24 weeks ) observed in 59 % of patients on anastrozole and 46 % on tamoxifen ( two-sided P = .0098 , retrospective analysis ) . Anastrozole had a significant advantage over tamoxifen in terms of TTP ( median TTP of 11.1 and 5.6 months for anastrozole and tamoxifen , respectively ; two-sided P = .005 ) . The tamoxifen  :  anastrozole  hazards ratio was 1.44 ( lower one-sided 95 % confidence limit , 1.16 ) . Both treatments were well tolerated . However , thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen ( 4.1 % v 8.2 % [ thromboembolic events ] and 1.2 % v 3.8 % [ vaginal bleeding ] , respectively ) . CONCLUSION Anastrozole satisfied the predefined criteria for equivalence to tamoxifen . Furthermore , we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole . These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer This paper is an overview of the new response evaluation criteria in solid tumours :  revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents BACKGROUND A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive , human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer . We performed a phase 3 study that was design ed to confirm and exp and the efficacy and safety data for palbociclib plus letrozole for this indication . METHODS In this double-blind study , we r and omly assigned , in a 2:1 ratio , 666 postmenopausal women with ER-positive , HER2-negative breast cancer , who had not had prior treatment for advanced disease , to receive palbociclib plus letrozole or placebo plus letrozole . The primary end point was progression-free survival , as assessed by the investigators ; secondary end points were overall survival , objective response , clinical benefit response , patient-reported outcomes , pharmacokinetic effects , and safety . RESULTS The median progression-free survival was 24.8 months ( 95 % confidence interval [ CI ] , 22.1 to not estimable ) in the palbociclib-letrozole group , as compared with 14.5 months ( 95 % CI , 12.9 to 17.1 ) in the placebo-letrozole group ( hazard ratio for disease progression or death , 0.58 ; 95 % CI , 0.46 to 0.72 ; P<0.001 ) . The most common grade 3 or 4 adverse events were neutropenia ( occurring in 66.4 % of the patients in the palbociclib-letrozole group vs. 1.4 % in the placebo-letrozole group ) , leukopenia ( 24.8 % vs. 0 % ) , anemia ( 5.4 % vs. 1.8 % ) , and fatigue ( 1.8 % vs. 0.5 % ) . Febrile neutropenia was reported in 1.8 % of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group . Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients ( 9.7 % ) in the palbociclib-letrozole group and in 13 patients ( 5.9 % ) in the placebo-letrozole group . CONCLUSIONS Among patients with previously untreated ER-positive , HER2-negative advanced breast cancer , palbociclib combined with letrozole result ed in significantly longer progression-free survival than that with letrozole alone , although the rates of myelotoxic effects were higher with palbociclib-letrozole . ( Funded by Pfizer ; PALOMA-2 Clinical Trials.gov number , NCT01740427 . ) PURPOSE To compare the clinical activity of the pure antiestrogen fulvestrant at 500 mg/mo ( double the approved dose ) with the aromatase inhibitor anastrozole as first-line endocrine therapy for advanced hormone receptor-positive breast cancer in postmenopausal women . PATIENTS AND METHODS FIRST ( Fulvestrant First-Line Study Comparing Endocrine Treatments ) is a phase II , r and omized , open-label , multicenter study of a fulvestrant high-dose ( HD ) regimen ( 500 mg/mo plus 500 mg on day 14 of month 1 ) versus anastrozole ( 1 mg/d ) . The primary efficacy end point was clinical benefit rate ( CBR ) , defined as the proportion of patients experiencing an objective response ( OR ) or stable disease for > or = 24 weeks . The primary analysis was performed 6 months after the last patient was r and omly assigned . RESULTS CBR was similar for fulvestrant HD ( n = 102 ) and anastrozole ( n = 103 ) , 72.5 % v 67.0 % , respectively ( odds ratio , 1.30 ; 95 % CI , 0.72 to 2.38 ; P = .386 ) . Objective response rate ( ORR ) was also similar between treatments : fulvestrant HD , 36.0 % ; anastrozole , 35.5 % . Time to progression ( TTP ) was significantly longer for fulvestrant versus anastrozole ( median TTP not reached for fulvestrant HD v 12.5 months for anastrozole ; hazard ratio , 0.63 ; 95 % CI , 0.39 to 1.00 ; P = .0496 ) . Duration of OR and CB also numerically favored fulvestrant HD . Both treatments were well tolerated , with no significant differences in the incidence of prespecified adverse events . CONCLUSION First-line fulvestrant HD was at least as effective as anastrozole for CBR and ORR and was associated with significantly longer TTP .  Fulvestrant HD was generally well tolerated , with a safety profile similar to that of anastrozole 
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Similarly , overall response rate and clinical benefit rate were higher for patients who received the combination therapy than for patients allocated to AI alone .
Conclusion The addition of CDK 4/6 inhibitors ( either abemaciclib , palbociclib , or ribociclib ) to an AI ( anastrozole or letrozole ) significantly improved PFS , overall response rate , and clinical benefit rate in comparison with a nonsteroidal AI alone