***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: Abstract Background Patient-reported outcomes are integral in benefit – risk assessment s of new treatment regimens . The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life ( QOL ) for patients with metastatic breast cancer ( MBC ) receiving first-line endocrine-based therapy ( palbociclib plus letrozole and letrozole alone ) . Patients and methods Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative ( HER2− ) MBC were r and omized 2 : 1 to palbociclib plus letrozole ( n = 444 ) or placebo plus letrozole ( n = 222 ) . Patient-reported outcomes were assessed at baseline , day 1 of cycles 2 and 3 , and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions ( EQ-5D ) question naires . Results As of 26 February 2016 , the median duration of follow-up was 23 months . Baseline scores were comparable between the two treatment arms . No significant between-arm differences were observed in change from baseline in FACT-Breast Total , FACT-General Total , or EQ-5D scores . Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm ( −0.256 versus −0.098 ; P = 0.0183 ) . In both arms , deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without . No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia . Conclusions Overall , women with MBC receiving first-line endocrine therapy have a good QOL . The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2− MBC compared with letrozole alone . Significantly greater delay in deterioration of health-related QOL was observed in patients without progression versus those who progressed and in patients with an objective response versus non-responders . Clinical Trials.gov : NCT01740427 ( https:// clinical trials.gov/ct2/show/NCT01740427 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 MONARCH 2 ( Clinical Trials.gov identifier : NCT02107703 ) compared the efficacy and safety of abemaciclib , a selective cyclin-dependent kinase 4 and 6 inhibitor , plus fulvestrant with fulvestrant alone in patients with advanced breast cancer ( ABC ) . Patients and Methods MONARCH 2 was a global , double-blind , phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy ( ET ) , ≤ 12 months from the end of adjuvant ET , or while receiving first-line ET for metastatic disease . Patients were r and omly assigned 2:1 to receive abemaciclib or placebo ( 150 mg twice daily ) on a continuous schedule and fulvestrant ( 500 mg , per label ) . The primary end point was investigator-assessed progression-free survival ( PFS ) , and key secondary end points included overall survival , objective response rate ( ORR ) , duration of response , clinical benefit rate , quality of life , and safety . Results Between August 2014 and December 2015 , 669 patients were r and omly assigned to receive abemaciclib plus fulvestrant ( n = 446 ) or placebo plus fulvestrant ( n = 223 ) . Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone ( median , 16.4 v 9.3 months ; hazard ratio , 0.553 ; 95 % CI , 0.449 to 0.681 ; P < .001 ) . In patients with measurable disease , abemaciclib plus fulvestrant achieved an ORR of 48.1 % ( 95 % CI , 42.6 % to 53.6 % ) compared with 21.3 % ( 95 % CI , 15.1 % to 27.6 % ) in the control arm . The most common adverse events in the abemaciclib versus placebo arms were diarrhea ( 86.4 % v 24.7 % ) , neutropenia ( 46.0 % v 4.0 % ) , nausea ( 45.1 % v 22.9 % ) , and fatigue ( 39.9 % v 26.9 % ) . Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective , significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost . Evidence for clinical benefit from new treatment options is derived from clinical research , in particular phase III r and omised trials , which generate unbiased data regarding the efficacy , benefit and safety of new therapeutic approaches . To date , there is no st and ard tool for grading the magnitude of clinical benefit of cancer therapies , which may range from trivial ( median progression-free survival advantage of only a few weeks ) to substantial ( improved long-term survival ) . Indeed , in the absence of a st and ardised approach for grading the magnitude of clinical benefit , conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented , discussed and promoted as major advances or ' breakthroughs ' . Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high- quality clinical trials , the European Society for Medical Oncology ( ESMO ) has developed a vali date d and reproducible tool to assess the magnitude of clinical benefit for cancer medicines , the ESMO Magnitude of Clinical Benefit Scale ( ESMO-MCBS ) . This tool uses a rational , structured and consistent approach to derive a relative ranking of the magnitude of clinical ly meaningful benefit that can be expected from a new anti-cancer treatment . The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care , helping to frame the appropriate use of limited public and personal re sources to deliver cost-effective and affordable cancer care . The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis BACKGROUND Whether progression-free survival ( PFS ) or overall survival ( OS ) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial . In some disease and treatment setting s , an improvement in PFS does not result in an improved OS . METHODS We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression ( SPP ) . We simulated r and omized clinical trials with two arms that had respective medians for PFS of 6 and 9 months . We assumed no treatment difference in median SPP . We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS . We compared the sample sizes required for PFS vs OS for various median SPP . We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS . All statistical tests were two-sided . RESULTS For a trial with observed P value for improvement in PFS of .001 , there was a greater than 90 % probability for statistical significance in OS if median SPP was 2 months but less than 20 % if median SPP was 24 months . For a trial requiring 280 patients to detect a 3-month difference in PFS  , 350 and 2440 patients , respectively , were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months . CONCLUSIONS Addressing SPP is important in underst and ing treatment effects . For clinical trials with a PFS benefit , lack of statistical significance in OS does not imply lack of improvement in OS , especially for diseases with long median SPP . Although there may be no treatment effect on SPP , its variability so dilutes the OS comparison that statistical significance is likely lost . OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long , such as longer than 12 months 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 . ) BACKGROUND In MONALEESA-2 , ribociclib plus letrozole showed improved progression-free survival compared with letrozole alone as first-line treatment for postmenopausal patients 
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Adding CDK4/6 inhibitors to ET in endocrine-sensitive ( HR 0.55 , 95 % CI 0.50–0.62 ) or endocrine-resistant setting ( HR 0.51 , 95 % CI 0.43–0.61 ) significantly improved the PFS of metastatic HR+/HER2− breast cancers regardless of menopausal status and site of metastasis .
Conclusion Emerging data provide a new st and ard treatment for advanced HR+/HER2− breast cancer , regardless of menopausal status , prior hormonal/chemotherapy treatments delivered , sites of metastasis .