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O27 - Clinical Trials and Practice (ID 142)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Other Topics
- Presentations: 1
- Moderators:J.S. Lee, J. Bishop
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Auditorium A, Level 1
O27.02 - Preliminary results from the FRAGMATIC trial: A randomised Phase III clinical trial investigating the effect of FRAGMin® Added to standard Therapy In patients with lung Cancer. (ID 1799)
16:15 - 17:45 | Author(s): S. Noble
Venous thromboembolism (VTE) is common in lung cancer patients and the incidence is increased by treatments including radiotherapy, surgery and chemotherapy. Research suggests a survival benefit in cancer patients receiving long term low moecular weight heparin (LMWH). LMWH may also have antimetastatic effects through the inhibition of P-selectin. This trial was developed to investigate whether or not adding LMWH to standard treatment increases overall survival. The study is funded by a research grant from Cancer Research UK (C13275/A5323) and free drug and an educational grant from Pfizer. The trial is sponsored by Velindre NHS Trust, and coordinated by the Wales Cancer Trials Unit, Cardiff, UK.
An open label, multi-centre, Phase III randomised controlled trial in patients with lung cancer comparing anticancer treatment according to local practice plus dalteparin (Fragmin®), with anticancer treatment alone. Eligible patients had a histopathological or cytological diagnosis of primary bronchial carcinoma (SCLC or NSCLC) within the previous 7 weeks, performance status 0, 1, 2 or 3 and were willing and able to inject daily subcutaneous injection. The dalteparin was given as a daily 5,000 IU subcutaneous injection for 24 weeks. The primary outcome measure is overall survival and the secondary outcome measures include toxicity, VTE-free survival, metastasis-free survival, quality of life, and cost utility. To detect an advantage of 5% in overall survival at 1 year (to 30%) a total of 2200 patients were required (1100 in each arm).
2202 patients were enrolled and randomised in 4 years. The two groups were well balanced for key variables. 60% were men; the median age was 65 years; 82% had NSCLC (5% Stages I and II, 38% Stage III, 57% Stage IV) and 18% SCLC (63% Extensive Disease); 85% had WHO PS 0 or 1; 95% received chemotherapy as first treatment. 56% of those in the dalteparin arm received at least 90 of the 168 planned injections. By 1/8/2013 there had been 1891 deaths recorded and, on advice from the Independent Data Monitoring Committee, the primary results have been released. There was no significant difference in overall survival (HR 0.97; 95% CI 0.89-1.06) nor in metastasis-free survival. Exploratory subgroup analyses do not suggest a significant survival advantage in any subgroup. Dalteparin use was not associated with a significant increase in major bleeding complications. There were 78 (7.1%) confirmed VTEs in the control group and 47 (4.1%) in the treatment group.
This large RCT which recruited mainly good PS lung cancer patients having chemotherapy, has confirmed that prophylactic dalteparin reduces the risk of VTE events without a significant increase in major bleeding. The baseline VTE risk of 7% and relative risk reduction of 40% are consistent with previous studies. There was no significant difference in overall survival. These results do not support a policy of routine prophylactic anticoagulation of all lung cancer patients undergoing chemotherapy.
P2.24 - Poster Session 2 - Supportive Care (ID 157)
- Event: WCLC 2013
- Type: Poster Session
- Track: Supportive Care
- Presentations: 2
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P2.24-025 - Applying the results of the FRAGMATIC trial to real life: longitudinal qualitative study exploring the experiences of patients partcipating in a randomised Phase III clinical trial investigating the effect of FRAGMin Added To standard therapy In lung Cancer (ID 1581)
09:30 - 16:30 | Author(s): S. Noble
Clinical data suggests low molecular weight heparin (LMWH) may produce a survival benefit when given to cancer patients. Several studies are being conducted in different cancer primaries to explore this hypothesis including FRAGMATIC, which will be presented at the World Lung Conference. The FRAGMATIC trial is an open label multi-centre Phase III randomised controlled trial in patients with lung cancer comparing anticancer treatment according to local practice plus dalteparin (Fragmin®), with anticancer treatment according to local practice alone. The primary outcome measure is overall survival and the secondary outcome measures include; toxicity, VTE-free survival, metastasis-free survival, quality of life, patient experience and cost utility. 2202 patients have been recruited in order to detect an advantage of 5% in overall survival at 1 year (to 30%). Fragmin is given as a daily subcutaneous injection for six months by the patients themselves or a willing partner/ carer. This may raise practical challenges regarding how applicable the results of the main trial will be to clinical practice especially with regard to quality of life and thus compliance. We conducted a longitudinal quality of life study to explore the experiences of patients participating in the FRAGMATIC trial to better inform the patient journey and practicalities of applying results to clinical practice.
Semi-structured interviews were held at up to three time points, with two groups of patients recruited from the intervention (n=4) and control (n=6) arms of the FRAGMATIC trial.A total of twenty interviews were analysed using Interpretative Phenomenological Analysis to identify emergent themes that reflect participants' lived experience. We report data focusing on participant views and experiences of self injection for six months.
No discernable difference in quality of life was identified between patients in the control or intervention arm who reported similar experiences of the cancer journey and its treatments. Patients on the intervention arm found daily Fragmin injections to be acceptable and a small consequence of having additional treatment as they saw it. Patients developed processes in order to administer Fragmin at similar times and described adaptive techniques to reduce discomfort and bruising. Minimal training was required to be able to inject Fragmin and few side effects were reported. The most common side effect was stinging which was short lived and bruising around injection sites. Patients reported these events did not impact upon quality of life. Overall, Fragmin was found to be an acceptable intervention, which did not pose any compliance problems.
The FRAGMATIC trail will report the impact of daily subcutaneous LMWH on overall survival in lung cancer. In this trial 1100 patients self injected Fragmin or had it administered to them. Based on qualitative interview data, Fragmin injections were well tolerated and the experiences of patients suggest that it would be relatively simple to introduce self-injecting into standard lung cancer therapy should the results of the FRAGMATIC study demonstrate a survival benefit.
P2.24-033 - The value of assessing muscle depletion in lung cancer (sarcopenia) rather than body surface area, in the work-up to chemotherapy. Reflections from a Systematic Review. (ID 2388)
09:30 - 16:30 | Author(s): S. Noble
Dosing of many chemotherapy drugs is currently based on body surface area (BSA), which is partly derived from body weight. However, BSA has been shown to result in large inter-patient variability in drug exposure. Another measurement of body composition is fat free mass (FFM), which includes hepatic, renal and muscle metabolic tissue. Depletion of FFM is termed sarcopenia, which in breast and renal cancer populations is associated with increased chemotherapy toxicity and time to disease progression. Sarcopenia can occur regardless of weight or BSA. In order to explore the value of FFM assessment in lung cancer patients undergoing chemotherapy, we performed a systematic review to explore this relationship. We present an analysis of relationships between sarcopenia, body weight, BSA, chemotherapy toxicities and outcomes in lung cancer patients.
Two search strings (‘muscle mass loss’ AND ‘lung cancer’) were used as a basis for formulating specific literature search strategies in five databases. We included all publication types and the search was limited to articles written in English. From this larger review, we then narrowed our focus to chemotherapy-specific studies.
Our systematic review of FFM loss in lung cancer consisted of 29 studies, from which 7 studies considered specifically the relationship between FFM and chemotherapy. One study of 250 obese patients found 15% were sarcopenic, FFM poorly correlated with BSA (r=0.37), and variation in FFM per unit of BSA could account for up to three-times variation of chemotherapy volume of distribution, potentially indicating increased risk of chemotherapy toxicity. A further population-based study (N=441) found 46.8% were sarcopenic, despite only 7.5% being underweight. A further two smaller studies (N=40, 41) found the prevalence of sarcopenia to be 61% and 46% (despite approximately half being overweight or obese). Prospective evaluation of the effect of chemotherapy on FFM in 3 small studies (N<22) showed no significant change. Sarcopenia was also associated with poorer performance status and reduced median survival.
A more refined understanding of body composition is needed in lung cancer patients, in order to minimise toxicities of chemotherapy, whilst ensuring optimal chemotherapy dosage. The current literature suggests that a more detailed prospective study is required in order to explore the validity and advantage of measuring FFM rather than BSA in lung cancer patients, in the work-up to chemotherapy. It also suggests that targeting sarcopenia may offer a novel approach to improving chemotherapy tolerance and overall survival.