EVALUATION/PRIORITIZATION CRITERIA: C, L, R, S *to meet requirement 1



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COMPENDIA TRANSPARENCY TRACKING FORM DATE: MAY 2015 PACKET: 111 DRUG: INDICATION: Vinorelbine Tartrate Malignant pleural mesothelioma COMPENDIA TRANSPARENCY REQUIREMENTS 1 Provide criteria used to evaluate/prioritize the request (therapy) 2 Disclose evidentiary materials reviewed or considered Provide names of individuals who have substantively participated in the review or disposition of the request and disclose their potential direct or indirect conflicts of interest 4 Provide meeting minutes and records of votes for disposition of the request (therapy) EVALUATION/PRIORITIZATION CRITERIA: C, L, R, S *to meet requirement 1 CODE EVALUATION/PRIORITIZATION CRITERIA A Treatment represents an established standard of care or significant advance over current therapies C Cancer or cancer-related condition E Quantity and robustness of evidence for use support consideration L Limited alternative therapies exist for condition of interest P Pediatric condition R Rare disease S Serious, life-threatening condition Note: a combination of codes may be applied to fully reflect points of consideration [eg, therapy may represent an advance in the treatment of a lifethreatening condition with limited treatment alternatives (ASL)] 2012 Truven Health Analytics Inc All rights reserved Page 1 of 6

EVIDENCE CONSIDERED: *to meet requirements 2 and 4 CITATION STUDY-SPECIFIC COMMENTS LITERATURE CODE Muers,MF, Stephens,RJ, Fisher,P, et al: Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial Lancet May 17, 2008; Vol 71, Issue 9625; pp 1685-1694 Stebbing,J: The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma Lung Cancer Jan 2009; Vol 6, Issue 1; pp 94-97 Zucali,PA: Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma Lung Cancer Jun 2014; Vol 84, Issue ; pp 265-270 Sorensen,JB: Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma British Journal of Cancer Jul 08, 2008; Vol 99, Issue 1; pp 44-50 This was a randomized-controlled trial Due to slow accrual, the trial was stopped early and didn't meet the original planned sample size of 840 patients The two chemo arms were combined and compared to active symptom control With a target of 420 patients, there was 76% power to detect a month benefit in OS with chemo This study was at low risk of bias associated with allocation concealment, lack of blinding, incomplete accounting of patients and outcome events, and selective outcome reporting The risk of bias associated with random sequence generation was unclear and not discussed in the paper S 2012 Truven Health Analytics Inc All rights reserved Page 2 of 6

Zucali,PA, Ceresoli,GL, Garassino,I, et al: Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma Cancer Apr 01, 2008; Vol 112, Issue 7; pp 1555-1561 Steele,JP: Phase II study of vinorelbine in patients with malignant pleural mesothelioma Journal of Clinical Oncology Dec 01, 2000; Vol 18, Issue 2; pp 912-917 Fennell,DA: Phase II trial of vinorelbine and oxaliplatin as firstline therapy in malignant pleural mesothelioma Lung Cancer Feb 2005; Vol 47, Issue 2; pp 277-281 Toyokawa,G, Takenoyama,M, Hirai,F, et al: Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy Int J Clin Oncol Aug 2014; Vol 19, Issue 4; pp 601-606 Maruyama,R: Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma Japanese Journal of Clinical Oncology Aug 2005; Vol 5, Issue 8; pp 4-48 2012 Truven Health Analytics Inc All rights reserved Page of 6

Stahel,RA, Weder,W, Lievens,Y, et al: Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, 4 treatment and follow-up Annals of Oncology May 2010; Vol 21, Issue SUPPL 5; pp v126-v128 Chen,SE and Pace,MB: Malignant pleural mesotheliomachen2012 Am J 4 Health Syst Pharm Mar 01, 2012; Vol 69, Issue 5; pp 77-85 Literature evaluation codes: S = Literature selected; 1 = Literature rejected = Topic not suitable for scope of content; 2 = Literature rejected = Does not add clinically significant new information; = Literature rejected = Methodology flawed/methodology limited and unacceptable; 4 = Other (review article, letter, commentary, or editorial) 2012 Truven Health Analytics Inc All rights reserved Page 4 of 6

CONTRIBUTORS: *to meet requirement PACKET PREPARATION DISCLOSURES EXPERT REVIEW DISCLOSURES Margi Schiefelbein, PA None Edward Balaban, DO None Stacy LaClaire, PharmD None Thomas Marsland, MD None Felicia Gelsey, MS None James E Liebmann, MD None Jeffrey A Bubis, DO Other payments: Dendreon Keith Thompson, MD None ASSIGNMENT OF RATINGS: *to meet requirement 4 EFFICACY STRENGTH OF COMMENTS RECOMMENDATION MICROMEDEX --- --- B Edward Balaban, DO Ineffective Class lll: Not Recommended No real data to suggest effectiveness N/A Thomas Marsland, MD Evidence is Inconclusive Class llb: Recommended, In Some Cases There is only a single, old study that only suggests minimal to no benefit for Vinorelbine Drug may help an occasional patient, but generally data do not support widespread use STRENGTH OF EVIDENCE N/A 2012 Truven Health Analytics Inc All rights reserved Page 5 of 6

James E Liebmann, MD Evidence is Inconclusive Class lll: Not Recommended Cisplatin and pemetrexed is currently the only standard regimen approved for treatment of mesothelioma While there have been many Phase ll trials of vinorelbine in this disease, all report limited activity The trial for review only included chemotherapy arms that did not show improved survival compared to supportive care, though subset analysis of the vinorelbine arm suggested an improvement in survival with that drug As the authors suggest, N/A that result is hypothesis generating, but not evidence for efficacy It is tempting to consider vinorelbine for patients not fit enough to receive cisplatin, but the current trial does not support that, since all patients in this trial were fit enough to receive cisplatin Hence, at present there are no data to support the use of vinorelbine in place of cisplatin and pemetrexed in the treatment of mesothelioma Jeffrey A Bubis, DO Ineffective Class lll: Not Recommended Vinorelbine has not been demonstrated to be an active agent in this clinical N/A scenario Keith Thompson, MD Ineffective Class lll: Not Recommended None N/A 2012 Truven Health Analytics Inc All rights reserved Page 6 of 6