***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 
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    Input: BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies PURPOSE Phase I data ( ASCEND-1 ) showed ceritinib  efficacy in patients with ALK-rearranged non-small-cell lung cancer ( NSCLC ) , regardless of brain metastases status and with or without prior therapy with an inhibitor of the ALK protein . Data are presented from a phase II trial ( ASCEND-2 ) in which ceritinib  efficacy and safety were evaluated in patients who had ALK-rearranged NSCLC previously treated with at least one platinum-based chemotherapy and who had experienced progression during crizotinib treatment as their last prior therapy . PATIENTS AND METHODS Patients with advanced ALK-rearranged NSCLC , including those with asymptomatic or neurologically stable baseline brain metastases , received oral ceritinib 750 mg/d . Whole-body and intracranial responses were investigator assessed ( according to RECIST version 1.1 ) . Patient-reported outcomes were evaluated with the Lung Cancer Symptom Scale and European Organisation for Research and Treatment of Cancer surveys ( the core-30 and the 13-item lung cancer-specific quality -of-life question naires ) . RESULTS All 140 patients enrolled had received two or more previous treatment regimens , and all patients had received crizotinib . The median duration of exposure and the follow-up time with ceritinib were 8.8 months ( range , 0.1 to 19.4 months ) and 11.3 months ( range , 0.1 to 18.9 months ) , respectively . Investigator-assessed overall response rate was 38.6 % ( 95 % CI , 30.5 % to 47.2 % ) . Secondary end points , all investigator assessed , included disease control rate ( 77.1 % ; 95 % CI , 69.3 % to 83.8 % ) , time to response ( median , 1.8 months ; range , 1.6 to 5.6 months ) , duration of response ( median , 9.7 months ; 95 % CI , 7.1 to 11.1 months ) , and progression-free survival ( median , 5.7 months ; 95 % CI , 5.4 to 7.6 months ) . Of 100 patients with baseline brain metastases , 20 had active target lesions at baseline ; investigator-assessed intracranial overall response rate was 45.0 % ( 95 % CI , 23.1 % to 68.5 % ) . The most common adverse events ( majority , grade 1 or 2 ) for all treated patients were nausea ( 81.4 % ) , diarrhea ( 80.0 % ) , and vomiting ( 62.9 % ) . Patient-reported outcomes showed a trend toward improved symptom burden . The global quality -of-life score was maintained during treatment . CONCLUSION Consistent with its activity in ASCEND-1 , ceritinib treatment provided clinical ly meaningful and durable responses with manageable tolerability in chemotherapy- and crizotinib-pretreated patients , including those with brain metastases Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer ( ALK-positive NSCLC ) eventually experience disease progression . We evaluated two regimens of brigatinib , an investigational next-generation ALK inhibitor , in crizotinib-refractory ALK-positive NSCLC . Patients and Methods Patients were stratified by brain metastases and best response to crizotinib . They were r and omly assigned ( 1:1 ) to oral brigatinib 90 mg once daily ( arm A ) or 180 mg once daily with a 7-day lead-in at 90 mg ( 180 mg once daily [ with lead-in ] ; arm B ) . Investigator-assessed confirmed objective response rate ( ORR ) was the primary end point . Results Of 222 patients enrolled ( arm A : n = 112 , 109 treated ; arm B : n = 110 , 110 treated ) , 154 ( 69 % ) had baseline brain metastases and 164 of 222 ( 74 % ) had received prior chemotherapy . With 8.0-month median follow-up , investigator-assessed confirmed ORR was 45 % ( 97.5 % CI , 34 % to 56 % ) in arm A and 54 % ( 97.5 % CI , 43 % to 65 % ) in arm B. Investigator-assessed median progression-free survival was 9.2 months ( 95 % CI , 7.4 to 15.6 ) and 12.9 months ( 95 % CI , 11.1 to not reached ) in arms A and B , respectively . Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42 % ( 11 of 26 patients ) in arm A and 67 % ( 12 of 18 patients ) in arm B. Common treatment-emergent adverse events were nausea ( arm A/B , 33%/40 % ) , diarrhea ( arm A/B , 19%/38 % ) , headache ( arm A/B , 28%/27 % ) , and cough ( arm A/B , 18%/34 % ) , and were mainly grade s 1 to 2 . A subset of pulmonary adverse events with early onset ( median onset : day 2 ) occurred in 14 of 219 treated patients ( all grade s , 6 % ; grade ≥ 3 , 3 % ) ; none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib . Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival ; 180 mg ( with lead-in ) showed consistently better efficacy than 90 mg , with acceptable safety Purpose Alectinib has shown activity in the CNS in phase I and II studies . To further evaluate this activity , we pooled efficacy and safety data from two single-arm phase II studies ( NP28761 and NP28673 ; Clinical Trials.gov identifiers : NCT01871805 and NCT01801111 , respectively ) in patients with ALK-positive non-small-cell lung cancer ( NSCLC ) . Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib ; all patients received alectinib 600 mg twice per day . The primary end point in both studies was independent review committee (IRC)-assessed objective response rate ( ORR ; by Response Evaluation Criteria in Solid Tumors [ RECIST ] version 1.1 ) . Additional end points ( all by IRC ) included CNS ORR ( CORR ) , CNS disease control rate ( CDCR ) , and CNS duration of response ( CDOR ) . Results One hundred thirty-six patients had baseline CNS metastases ( 60 % of the overall study population s ) ; 50 patients ( 37 % ) had measurable CNS disease at baseline . Ninety-five patients ( 70 % ) had prior CNS radiotherapy ; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib .  Median follow-up time was 12.4 months ( range , 0.9 to 19.7 months ) . For patients with baseline measurable CNS disease , IRC CORR was 64.0 % ( 95 % CI , 49.2 % to 77.1 % ) , CDCR was 90.0 % ( 95 % CI , 78.2 % to 96.7 % ) , and median CDOR was 10.8 months ( 95 % CI , 7.6 to 14.1 months ) . For patients with measurable and /or nonmeasurable baseline CNS disease , IRC CORR was 42.6 % ( 95 % CI , 34.2 % to 51.4 % ) , CDCR was 85.3 % ( 95 % CI , 78.2 % to 90.8 % ) , and median CDOR was 11.1 months ( 95 % CI , 10.3 months to not evaluable ) . CORR was 35.8 % ( 95 % CI , 26.2 % to 46.3 % ) for patients with prior radiotherapy ( n = 95 ) and 58.5 % ( 95 % CI , 42.1 % to 73.7 % ) for patients without prior radiotherapy ( n = 41 ) . As previously reported , alectinib was well tolerated , regardless of baseline CNS disease . Conclusion Alectinib showed good efficacy against CNS metastases , in addition to systemic activity , in crizotinib-refractory ALK-positive NSCLC BACKGROUND Osimertinib ( AZD9291 ) is an oral , potent , irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations , and the EGFR Thr790Met resistance mutation . We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer ( NSCLC ) , who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor . METHODS In this phase 2 , open-label , single-arm study ( AURA2 ) , patients aged at least 18 years with central ly confirmed EGFR Thr790Met-positive mutations , locally advanced or metastatic ( stage IIIB/IV ) NSCLC who progressed on previous EGFR tyrosine-kinase inhibitor therapy  received osimertinib 80 mg orally once daily ; treatment could continue beyond progression if the investigator observed a clinical benefit . Patients with asymptomatic , stable CNS metastases not requiring steroids were allowed to enrol . The primary endpoint was the proportion of patients achieving an objective response by blinded independent central review using Response Evaluation Criteria in Solid Tumors , version 1.1 . Response endpoints were assessed in the evaluable for response analysis set ( ie , all patients who received at least one dose of osimertinib and had measurable disease at baseline according to blinded independent central review ) . Other endpoints and safety were assessed in all patients receiving at least one osimertinib dose ( full analysis set ) . The study is ongoing and patients are still receiving treatment . This study is registered with Clinical Trials.gov , number NCT02094261 . FINDINGS Between May 20 , 2014 , and Sept 12 , 2014 , 472 patients were screened , of whom 210 started osimertinib treatment between June 13 , 2014 , and Oct 27 , 2014 ; 11 patients were excluded from the evaluable for response analysis set ( n=199 ) due to absence of measurable disease at baseline 
    Output:
    
Conclusions and Relevance Findings reported herein support a potential role for osimertinib in the treatment of patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib .