ROMANA 3: A phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Background: Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. Patients and methods: ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤ 2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12-24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24 weeks). Results: Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥ 3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P < 0.0001) and improved anorexia-cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group. Conclusion: During the 12-24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved with anamorelin

Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

Effect of an exercise training intervention with resistance bands on blood cell counts during chemotherapy for lung cancer: a pilot randomized controlled trial

PURPOSE: Chemotherapy for lung cancer can have a detrimental effect on white blood cell (WBC) and red blood cell (RBC) counts. Physical exercise may have a role in improving WBCs and RBCs, although few studies have examined cancer patients receiving adjuvant therapies. The purpose of this pilot trial was to examine the effects of an exercise intervention utilizing resistance bands on WBCs and RBCs in lung cancer patients receiving curative intent chemotherapy. METHODS: A sample of lung cancer patients scheduled for curative intent chemotherapy was randomly assigned to the exercise intervention (EX) condition or usual care (UC) condition. The EX condition participated in a three times weekly exercise program using resistance bands for the duration of chemotherapy. RESULTS: A total of 14 lung cancer patients completed the trial. EX condition participants completed 79% of planned exercise sessions. The EX condition was able to maintain WBCs over the course of the intervention compared to declines in the UC condition (p = .008; d = 1.68). There were no significant differences in change scores in RBCs. CONCLUSIONS: Exercise with resistance bands may help attenuate declines in WBCs in lung cancer patients receiving curative intent chemotherapy. Larger trials are warranted to validate these findings. Ultimately these findings could be informative for the development of supportive care strategies for lung cancer patients receiving chemotherapy. TRIAL REGISTRATION: Clinical Trials Registration #: NCT01130714

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data

Strength in numbers : patient experiences of group exercise within hospice palliative care

Background: Exercise is increasingly recognized as a core component of palliative rehabilitation. The group exercise model is often adopted as a means of reaching more patients with limited resource. Despite the growth of quantitative research examining this area of practice, few qualitative studies have looked at the patient experience of participating in group exercise in a palliative setting, and most exclude patients with a non-cancer diagnosis. Methods: The aim of this study was to explore patients’ experiences of participating in group exercise classes in a hospice setting. In this qualitative, phenomenological study, nine patients participating in a group exercise programme at a South London hospice completed semi-structured interviews. Participants were purposively sampled by gender, age, ethnicity and diagnosis; to include diagnoses across cancer, respiratory and neurological conditions. Transcripts were interpreted using thematic analysis. Results: All patients reported positive experiences of participating in group exercise classes. Improvements reported in physical function had a positive effect on ability to complete activities of daily living and enhanced patient mood. Other reported psychosocial benefits included: promotion of self-management; space and opportunity for reflection; supportive relationships; sharing of information; and a deeper appreciation of patients’ own abilities. Conclusion: This study highlights the positive experiences and value of group exercise classes to groups of people with diverse cancer and non-cancer conditions. The physical, emotional and psychosocial benefits suggest hospices and other palliative services should explore similar programmes as part of their rehabilitation services. The recognition that exercise groups can be mixed and need not be bespoke to one condition has positive cost and staff resource ramifications