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R.J. Gralla
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MTE 28 - Need for Team Building in Caring for Patients with Thoracic Malignancies (Ticketed Session) (ID 80)
- Event: WCLC 2015
- Type: Meet the Expert (Ticketed Session)
- Track: Nursing and Allied Professionals
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 07:00 - 08:00, 102+104+106
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MTE28.02 - Need for Team Building in Caring for Patients with Thoracic Malignancies (ID 2016)
07:30 - 08:00 | Author(s): R.J. Gralla
- Abstract
- Presentation
Abstract not provided
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ORAL 29 - MASCC-IASLC Joint Session: Palliative and Supportive Care (ID 136)
- Event: WCLC 2015
- Type: Oral Session
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:A. Molasiotis, P. Van Houtte
- Coordinates: 9/08/2015, 16:45 - 18:15, 708+710+712
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ORAL29.05 - Discussant for ORAL29.01, ORAL29.02, ORAL29.03, ORAL29.04 (ID 3543)
17:29 - 17:39 | Author(s): R.J. Gralla
- Abstract
- Presentation
Abstract not provided
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ORAL 31 - PD1 Axis Inhibition (ID 143)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:J. Weiss, B. Luey
- Coordinates: 9/09/2015, 16:45 - 18:15, Four Seasons Ballroom F1+F2
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ORAL31.03 - Evaluation of Disease-Related Symptoms in Patients with Advanced Squamous Non-Small Cell Lung Cancer Treated with Nivolumab or Docetaxel (ID 743)
17:07 - 17:18 | Author(s): R.J. Gralla
- Abstract
- Presentation
Background:
The CheckMate 017 (NCT01642004) randomized, open-label, global phase 3 study evaluated efficacy and safety of second-line nivolumab vs docetaxel in patients with advanced squamous (SQ) non-small cell lung cancer (NSCLC). Overall survival was significantly superior and duration of treatment longer for nivolumab vs docetaxel. The study also evaluated disease-related symptoms using the Lung Cancer Symptom Scale (LCSS).
Methods:
The LCSS includes 100 mm visual analog scales for 6 major lung cancer symptoms plus three global items evaluating the impact of symptoms; 0 represents the least severity and 100 the greatest severity. Assessment was performed every 4 weeks for nivolumab and every 3 weeks for docetaxel for the first 6 months on treatment, followed by every 6 weeks for the remainder of the treatment period for both study arms. Following treatment discontinuation, the LCSS also was assessed at two follow-up visits. The LCSS average symptom burden index (ASBI) was computed from the 6 individual symptom scores. Mean baseline and mean change from baseline of the LCSS ASBI at each assessment were summarized by treatment group. A study secondary endpoint was to estimate the proportion of patients whose LCSS ASBI showed a clinically meaningful improvement by week 12 (10 point or greater decrease, the minimally important difference [MID]), which was based on all randomized patients.
Results:
Patient baseline characteristics were generally balanced across treatment groups. LCSS completion rates for baseline and at least one subsequent assessment were 68.9% and 62.8% for nivolumab and docetaxel, respectively. Completion rates remained relatively consistent throughout assessments and by treatment arm. Baseline LCSS ASBI values were similar for nivolumab (29.6; standard deviation [SD] 16.4) and docetaxel (29.6; SD 14.7). By week 12, 20.0% (27/135; 95% CI: 13.6, 27.7) of nivolumab patients demonstrated clinically meaningful symptom improvement compared to 21.9% (30/137; 95% CI: 15.3, 29.8) of docetaxel patients. Examining mean changes from baseline in patients’ LCSS ASBIs at each assessment, the nivolumab group demonstrated statistically significant improvements from baseline at each assessment from week 12 through week 54, after which sample sizes dropped to fewer than 10 patients; from week 40 through 54, the mean improvements exceeded the MID. In contrast, docetaxel patients remaining on treatment had no statistically significant changes in LCSS ASBI through week 18, after which the sample dropped to fewer than 10 patients. In the two follow-up visits after treatment discontinuation, the mean of the LCSS ASBI for both nivolumab and docetaxel patients indicated similar worsening of symptoms relative to baseline (range, 5.5–9.5); for docetaxel patients, the differences from baseline were statistically significant.
Conclusion:
By week 12, the proportion of patients showing meaningful symptom improvement was similar for both the nivolumab and docetaxel groups. However, the overall average symptom burden while on nivolumab improved from baseline over most of the year of available follow up, while average symptom burden for docetaxel patients remained stable relative to baseline during their shorter time on treatment. These results show statistically and clinically significant reductions from baseline in lung cancer symptoms for patients with squamous NSCLC treated with second-line nivolumab.
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P1.11 - Poster Session/ Palliative and Supportive Care (ID 229)
- Event: WCLC 2015
- Type: Poster
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.11-005 - Enhancing Evaluation of Cancer Cachexia in Patients with NSCLC by Assessing Change in Skeletal Muscle Mass at the L1 Level on Routine Chest CT (ID 2761)
09:30 - 09:30 | Author(s): R.J. Gralla
- Abstract
Background:
Cancer cachexia (CC) and sarcopenia occur in up to 60% of patients with lung cancer. With better knowledge of the pathophysiology leading to cancer cachexia, multiple recent therapeutic trials have been directed at these mechanisms. Additionally, it is clear that cancer cachexia is associated with several negative outcomes. Inherent in all studies for this problem, is the ability to measure components of cancer cachexia, such as skeletal muscle mass (SMM). SMM assessment by CT scanning (SD <1.2kgs) is more accurate than either Dual X ray absorptiometry (DXA, SD 3kgs) or than bioelectrical impedance (SD 9.3kgs). A single slice on CT at the third lumbar vertebra (L3) correlates highly (r=0.924) with total body SMM in healthy individuals. While CT measurement at L3 is often used in cancer cachexia trials, the problem exists that routine chest CT scans rarely extend to L3; thus routine chest CTs will not allow inclusion of most patients. Importantly, prior studies in normal subjects demonstrated high correlation (r = 0.903) of SMM measurement at L1 with L3; however, the utility and feasibility of L1 measurement of SMM has not been assessed in patients with cancer.
Methods:
We enlisted patients with NSCLC and performed SMM measurements at L1 using Slice-O-Matic software for muscle mass in the Hounsfield unit range of -29 to +150. Patients were assessed for accuracy of using the L1 level for imaging quality and the ability to use the software properly.
Results:
56 patients with NSCLC (99 CT assessments) were enlisted at three institutions. Characteristics: 45% female; medians: age 60, KPS 80%; BMI 24.96, weight 72.38 kg, SMM index 58.89. Sarcopenia was detected in 29% of patients (58% of males <55.5 cm2/M2; 6% of females <38.5cm2/M2) with all having normal or overweight BMI. Overall, of the 99 CT images, 92.9% (95% CI = 88%-98%) included L1. 5 additional images (5%) were difficult to evaluate for SMM due to ascites or effusions; also, 1 patient was too obese for proper imaging; 2 had poor quality scans. Importantly, inclusion of L1 differed among the 3 institutions ranging from 80.6% to 97.2%. Also noted, as previously reported with assessment at L3 (r = 0.35), the correlation of BMI with SMM in this study at L1 was low (r = 0.36) as well.
Conclusion:
This study indicates that: 1) SMM assessment at L1 is achievable on routine chest CT in patients with lung cancer, with 93% of patients having images at this level, and 93% have acceptable quality for SMM evaluation; 2) although L1 is included in the majority of patients at all 3 institutions, this may vary by different radiologic protocols; 3) the low correlation and poor sensitivity of BMI to identify muscle mass loss is equally demonstrated at both L3 and L1, and 4) use of L1 enhances patient evaluation for SMM without needing additional testing or radiation exposure, and allows many more patients with NSCLC to have assessment of SMM in clinical trials and patient management. Funding in part: NIH/NCI 1 R01 CA157409-01A1
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-040 - Prospective Evaluation of Changes in Cancer Cachexia in NSCLC in Patients given Chemotherapy by Correlating Skeletal Muscle Mass with PRO Results (ID 2845)
09:30 - 09:30 | Author(s): R.J. Gralla
- Abstract
Background:
Cancer cachexia and sarcopenia are common in lung cancer, and are associated with poor outcomes. Several recent interventional trials in cancer cachexia in patients with lung cancer have endeavored to improve skeletal muscle mass (measured by skeletal muscle mass index – SMI - using DXA or CT) and to correlate changes with functional outcomes of benefit to the patient. While functional tests such as stair climb power and hand grip strength have been used, these measures are neither sufficiently sensitive in patients with cancer, nor do they evaluate outcomes demonstrated to be valuable to patients. Patient Reported Outcomes (PROs) such as EORTC, FACT and others, have been collected, but specific components useful to patients have not been identified as ones correlating highly with SMI. Recent large studies at baseline using the 3-Item Global Index (3IGI) of the Lung Cancer Symptoms Scale (LCSS) quality of life and functional measure found strong correlations predicting survival in non-small cell lung cancer (N = 602) and in mesothelioma (N = 444); thus the 3IGI appears to be a good factor for associating PROs with SMI changes (Symanowski ASCO 2014; Gralla ASCO 2014). Additionally, over 90% of patients with NSCLC have expressed that parameters such as activity level and quality of life (included in the 3IGI) are of great importance to them.
Methods:
The LCSS was measured every 3 weeks in patients with a minimum KPS = 60 who were receiving chemotherapy. Correlations of SMI changes with 3IGI scores were made at baseline (at the time of initiation of chemotherapy) and at a median of 14 weeks in patients with Stage IIIB or IV NSCLC. SMI was measured by CT (Slice-O-Matic software) at the L1 vertebral level. A change in SMI by ± 4% was considered a threshold change of importance.
Results:
We have analyzed 24 patients to date (50% female; medians: age 57, KPS 80%; baseline: BMI 24.3, SMI 59.9, with 38% of males < 55.4 SMI). 19 patients are evaluable at this time. 42% of patients had a change in SMI by ± 4%; of these 75% had either improvement or worsening of the 3IGI in the direction expected from the change in SMI (improved 3IGI with increased SMI; worsened 3IGI with decreased SMI). No clear relationship in SMI was observed with response to chemotherapy thus far in the analysis.
Conclusion:
These results suggest: 1) the 3IGI may be useful in identifying both positive and negative changes in SMI, when using a 4% threshold change; 2) while we continue to enlist patients in this study, a confirmatory larger evaluation should be conducted; and 3) no measure should be used in practice or clinical trials of cancer cachexia or sarcopenia unless it has demonstrated validity in patients with cancer.
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P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.08-014 - COMMAND: A Phase 2 Randomized, Double-Blind, Study of Defactinib (VS-6063) as Maintenance Therapy in Malignant Pleural Mesothelioma (ID 2847)
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. Median OS with frontline chemotherapy of pemetrexed/cisplatin (pem/cis) is ~12 months. There is no established second line therapy. Pem/cis has been shown to enrich cancer stem cells (CSCs) in tumors. Focal adhesion kinase (FAK) inhibitors have been found to decrease CSCs in mesothelioma models. The use of a FAK inhibitor in a maintenance setting after frontline chemotherapy may therefore extend survival of MPM patients. Furthermore, approximately 40% of MPM tumors exhibit disruption of the NF2 tumor suppressor gene by mutation and/or deletion resulting in lack of expression of functional merlin protein. Mesothelioma cell lines that lack merlin are more sensitive to FAK inhibitors than those with wild type merlin. This Phase 2 study will determine if defactinib (VS-6063), an oral inhibitor of FAK, provides superior clinical benefit compared with placebo as maintenance treatment in patients with MPM following frontline pem/platinum therapy.
Methods:
COMMAND is a multinational, randomized, double-blind, placebo-controlled trial. Approximately 370 patients with PR or SD following ≥4 cycles of frontline pem/platinum therapy will be enrolled. Patients will receive defactinib 400 mg BID or matched placebo. Randomization will be stratified by merlin status, as determined by immunohistochemistry. Primary endpoints include OS and PFS. An adaptive enrichment design at the interim analysis (projected to occur in Q2 2015) may restrict patients to those with low merlin protein expression if greater benefit is observed among this subpopulation. Secondary endpoints include patient-reported outcomes, objective response and safety and tolerability. The study is currently enrolling across 15 countries. Clinical trial: NCT01870609.
Results:
Not applicable
Conclusion:
Not applicable
