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R.J. Gralla



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    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P2.14-014 - A Phase 2 Randomized, Double-blind, Placebo-Controlled, Multicenter Study of VS-6063 as Maintenance Therapy in Subjects with Malignant Pleural Mesothelioma which has Not Progressed on at least 4 Cycles of Pemetrexed/Platinum therapy (ID 3375)

      09:30 - 09:30  |  Author(s): R.J. Gralla

      • Abstract

      Background
      Malignant pleural mesothelioma (MPM) is an aggressive tumor in the pleural lining of the lung usually caused by asbestos exposure. Median OS following frontline chemotherapy with pemetrexed/cisplatin is ~12 months. There is no established second line therapy. Approximately 50% of MPM patients exhibit homozygous disruption of the NF2 tumor suppressor gene by mutation and/or deletion resulting in lack of expression of functional merlin protein. Preclinical data have indicated that mesothelioma cell lines that lack NF2/Merlin are especially sensitive to focal adhesion kinase (FAK) inhibition in both cellular and animal models. Interestingly, pemetrexed and cisplatin increase cancer stem cells (CSCs), while FAK inhibitors have been found to decrease CSCs in mesothelioma models. Given the sensitivity of mesothelioma cells lacking NF2/Merlin and the effect on CSCs, the use of a FAK inhibitor in a maintenance setting after first line chemotherapy may be an attractive strategy to extend survival of MPM patients. VS-6063 is an orally bioavailable selective inhibitor of FAK. In a phase 1 trial VS-6063 was generally well tolerated, with grade 1/2 nausea, vomiting and fatigue as the most frequent adverse events (Jones SF J Clin Oncol 2011 29:1 suppl; abstr 3002).

      Methods
      A multinational, randomized, double-blind, placebo controlled, phase 2 clinical trial was designed to determine if VS-6063 provides superior clinical benefit compared with placebo as a maintenance treatment in patients with MPM following frontline therapy with pemetrexed/platinum therapy. The study aims to assess whether VS-6063 improves median OS and median PFS over placebo. Randomization will be stratified by Merlin status (high versus low) and patients will receive either VS-6063 400mg BID continuously or matched placebo (1:1). The study follows an adaptive enrichment design where, pending results from an interim analysis, sampling may be restricted to patients with low Merlin protein expression if promising results are observed among the subpopulation. Approximately 370 eligible patients with pathologically confirmed MPM, who have PR or SD following at least 4 cycles of pemetrexed with either cisplatin or carboplatin, Karnofsky PS ≥70%, will be enrolled. Patients will continue treatment until disease progression. Archival tumor tissue will be used for the analysis of Merlin status and is therefore required for participation. Secondary endpoints include patient-reported outcomes of health-related quality of life and disease- or treatment-related symptoms utilizing the LCSS-meso scale, objective response and safety and tolerability. Clinical trial information: NCT01870609.

      Results
      not applicable

      Conclusion
      not applicable

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-035 - Evaluating health related quality of life and symptoms by using the electronic (ePRO) version of the LCSS (eLCSS-QL) in a 622 patient prospective multinational NSCLC trial (AP-QL Trial) with good cross-cultural reliability. (ID 2397)

      09:30 - 09:30  |  Author(s): R.J. Gralla

      • Abstract

      Background
      Major goals in advanced NSCLC include accurate evaluation of survival and quality of life. Few trials evaluate both of these major endpoints well. In many studies, only a minority of patients have quality of life and other patient reported outcomes (PROs) such as symptoms systematically followed over time, which decreases the value of the assessment of the treatment. Prior studies have identified barriers to measuring quality of life in clinical trials and in practice. To overcome these barriers, we used a computer-assisted version of the validated LCSS measure and tested this prospectively in a large study in patients with Stage IV and IIIB NSCLC. The eLCSS-QL requires only two minutes for completion of the patient version and proved to be highly acceptable in earlier studies (Hollen, Supp Care Cancer 2012).

      Methods
      This trial was conducted at 65 sites in 9 Asian countries. 622 patients received first-line treatment with docetaxel -based chemotherapy. Patient demographics included: 70% male; 65% adenocarcinoma; median: KPS = 90; ECOG = 1 (27% ECOG 0). Stages: IV (72%), IIIB (28%). 84% had two or more major symptoms. 80% received combination chemotherapy with cisplatin (52%) or carboplatin (28%). The eLCSS-QL was completed every 3 weeks at the clinic. We also surveyed 98 physicians and nurses treating these patients regarding their experiences concerning communication, usefulness and acceptability of the eLCSS-QL.

      Results
      Ninety-seven percent of patients completed the eLCSS-QL at baseline; 90% completed follow-up evaluations. Over 90% found the eLCSS-QL easy to use and acceptable to complete at each visit. More than 80% of patients reported increased awareness of symptoms and that the quality of life evaluation made it easier to speak with doctors and nurses. 1% refused eLCSS-QL completion. Of physicians and nurses, more than 90% found the eLCSS-QL easy to use and increased symptom awareness; 80% reported improved communication, enhanced satisfaction with the patient visit, and would recommend its use to others. Nearly 90% of physicians reported they could identify benefit from chemotherapy earlier; 76% would order fewer imaging tests and 80% said the eLCSS-QL could save time. Cross-cultural testing was performed in this 9 nation trial. Cronbach’s alpha scores were high for each country, and exceeded 0.85 overall, demonstrating good cross-cultural reliability. Treatment outcomes: major response rate 37%; median survivals: 13.9 months (docetaxel + cisplatin), 12.7 months (docetaxel + carboplatin).

      Conclusion
      Placing the well validated LCSS onto an electronic platform (eLCSS-QL) helped overcome barriers to evaluating QL in this large clinical trial, with 90% of patients completing baseline and repeated QL measures. Patients, physicians, and nurses all found the eLCSS-QL to be highly acceptable and easy to use. The good cross-cultural aspects of the eLCSS-QL indicate that the electronic platform is particularly suitable for multinational trials. This large prospective trial demonstrates that improved compliance with quality of life and PRO evaluation is feasible and can easily be accomplished in large clinical trials. Additionally, the electronic format enhances the potential for the use of PROs in decision making in clinical practice.