Background

Antiemetic guidelines universally recommend the combination of an NK₁ receptor antagonist (NK₁RA), a 5-HT₃RA, and dexamethasone (DEX) for patients receiving highly emetogenic chemotherapy (HEC). NEPA is the first oral fixed combination of an NK₁RA (netupitant) and a 5-HT₃RA (palonosetron, PALO). The approval of oral NEPA in the United States/Europe was based on studies demonstrating superiority of NEPA compared to oral PALO. In a recent head-to-head trial in Asia NEPA showed comparable efficacy/safety to a 3-day regimen of APR/GRAN. This is a pre-specified analysis of the efficacy of NEPA vs APR/GRAN in the Chinese patients in that study.

Methods

Chemotherapy-naïve solid tumor cancer patients in this randomized double-blind, parallel group study received either a single oral dose of NEPA prior to cisplatin-based HEC or a 3-day regimen of APR/GRAN, both with oral DEX on days 1-4. The efficacy endpoint evaluated was complete response (no emesis/no rescue medication) during the acute (0-24h), delayed (25-120h) and overall (0-120h) phases post-chemotherapy for the full analysis set (FAS). The risk difference for NEPA – APR/GRAN and associated 95% confidence intervals (CI) were analyzed using the Cochran-Mantel-Haenszel test.

Results

667 (81%) of the total FAS population (n = 828) were Chinese. Groups were comparable in this subset (NEPA/APR): most were male (69.0/69.5%), mean age 54.4/54.9 years, ECOG 0-1 (98.2/97.6%), lung cancer (70.9/67.4%). Response rates were similar for the treatment groups.Table: 501O

Conclusions

Oral NEPA administered only on day 1 showed comparable efficacy to a 3-day APR/GRAN regimen in Chinese patients receiving HEC. As a fixed oral combination of an NK₁RA and 5HT₃RA in a single capsule given once/cycle, NEPA offers patients a convenient effective prophylactic antiemetic.

Legal entity responsible for the study

Helsinn Healthcare, SA, Lugano, Switzerland

Funding

Helsinn Healthcare, SA

Disclosure

L. Zhang: Consultant for MSD; research funding from Helsinn, Lilly, and MSD, S. Lu: Consultant for Boehringer and Roche; speaker’s bureau for Lilly; travel reimbursed by Hutchison and Medipharm Limited, S. Chessari, C. Lanzarotti: Employee of Helsinn Healthcare, K. Jordan: Consultant for Helsinn Healthcare, Merck, MSD and Tesaro; travel reimbursed by MSD, M. Aapro: Consultant/investigator for Helsinn Healthcare, Merck and Tesaro

All other authors have declared no conflicts of interest.

Background

Recent randomized clinical trials (RCTs) have demonstrated benefits of various pharmacologic interventions for cachexia in improving weight and appetite. However, their comparative efficacy and safety are not available. Therefore, we conduct a systematic review and network-meta-analysis to evaluate the relative efficacy and safety of the pharmacologic interventions for cachexia.

Methods

PubMed, EmBase, Cochrane, and ClincalTrials.gov were searched for RCTs until October 2016. Key outcomes were total body weight (TBW) improvement and appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias of all RCTs. Network meta-analysis was performed to estimate relative magnitude of weight gain and appetite score increased at 8 weeks of all interventions, presented as mean difference (MD) or standardized mean difference with 95% confidence interval (CI). To rank the intervention hierarchy in the network meta-analysis, the rankograms, surface under the cumulative ranking (SUCRA) curves, and mean ranks were estimated.

Results

73 RCTs involving 9,615 patients with 12 therapeutic options were included. Majority is cancer patients (6,335), while 2,324 were HIV patients. Compared to placebo, corticosteroids, megace-H-com, megace-H and androgen were significantly associated with MD of TBW of 6.23 (95%CI 1.91, 10.56), 3.73 (95%CI 1.58, 5.88), 2.80 (95%CI 1.46, 4.13) and 1.47 (95%CI 0.31, 2.63) kg, respectively. For appetite improvement, megace-L, megace-H, medroxyprogesterone, androgen, megace-H-com, and ghrelin mimetics had significantly improved standardized APP score, compared to placebo. These score improvements were also reported earlier than 8 weeks in most appetite stimulants (ghrelin, megace-L, megace-H, and medroxyprogesterone). There is no significantly difference in serious ADRs as compared to the placebo.

Conclusions

This network meta-analysis suggests that appetite stimulants may offer superior benefits in the treatment of cachexia. Nonetheless, the comparative studies to compare safety and efficacy is warranted to better manage cachexia.

Clinical trial identification

Not applicable

Legal entity responsible for the study

Suphat Subongkot

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Chemotherapy-induced alopecia (CIA) is one of the most severe side effects breast cancer patients become distressed about. This study aimed to evaluate of the impact of a topical lotion on hair thickness and density among breast cancer survivors who had permanent chemotherapy-induced alopecia (PCIA).

Methods

This was a double-blind, randomized controlled trial. Patients self-administered the study product or placebo twice per day (morning, evening) for 6 months from February to December 2016. Changes of hair density and thickness were measured using a noninvasive bioengineering device, and CIA distress and body image, using standardized questionnaires, were assessed at 3 and 6 months after randomization. All analyses were conducted by the intention-to-treat principle.

Results

A total of 35 patients were randomized to intervention (n = 18) or placebo (n = 17) group. Intervention groups were older (52.1 (±6.8) than control groups [41.6 (±7.8), P < 0.001. Mean hair thickness (SD) at baseline was 49.9 (±12.7) and 48.1 (±8.4) µm in the intervention and the placebo groups, respectively (P-value 0.64). The corresponding values for hair density were 97.6 (±6.4) and 126.8 (±30.3) hairs/cm², respectively. After 6 month intervention, hair thickness had increased by 19.8% and 35.6% compared with baseline in the intervention and control groups, respectively. The corresponding values for hair density were 34.7% and 24.9%, respectively (P-value 0.37). Similar findings were observed after adjusting participants’ age.

Conclusions

In this pilot study, we showed the feasibility and longitudinal changes associated with a topical lotion to increase hair thickness and density among breast cancer survivors.

Clinical trial identification

NCT02605629

Legal entity responsible for the study

Samsung Medical Center

Funding

Legacy Healthcare SA

Disclosure

All authors have declared no conflicts of interest.

Background

Phlebitis is a very common side effect of continuous intravenous infusion of 5-fluorouracil via the peripheral veins. We evaluated the preventive effects of topical steroid application on fluorouracil-induced phlebitis in a randomized, double-blind, placebo-controlled trial.

Methods

Patients were randomly selected to receive either petroleum jelly plus steroid ointment (steroid group) or petroleum jelly ointment only (placebo group) at the Kyoto University Hospital. The main eligibility criteria were as follows: planned to undergo at least 1 course of cisplatin and 5-fluorouracil (CF) therapy; planned to receive anticancer drugs via the peripheral veins; not requiring steroid ointment on the arm (e.g., dermatitis treatment); and provided signed informed consent. Patients applied the ointments twice daily (morning and evening) during CF therapy. We assessed pigmentation and induration 24 hours and 1 month after CF therapy. To assess the effectiveness of petroleum jelly itself, the effects of the placebo and historical control (n = 14, no ointment) were also compared. The Fisher’s exact test (incidence) and log-rank test (time to events) were used for statistical analysis.

Results

We randomly assigned 46 patients to the steroid and placebo groups (n = 23 each). All patients applied their respective ointments. Forty-five subjects were included in the analysis, excluding 1 patient in the placebo group who applied the steroid ointment due to extravasation. The incidence of clinically significant phlebitis was lower in the steroid than in the placebo group (pigmentation: 24 hours, 0% vs. 22%, P = 0.05; 1 month, 18% vs. 48%, P = 0.06; induration: 24 hours, 0% vs. 0%, P = 1.00; 1 month, 5% vs. 39%, P = 0.01). Pigmentation occurred earlier in the placebo group (placebo, median 6 days; steroid, median 13.5 days; P = 0.363). The incidence rates of phlebitis were significantly lower in the placebo group than in the historical control (52% vs. 86%; P = 0.04).

Conclusions

Patients receiving petroleum jelly plus steroid topical ointment clinically showed alleviation of CF-therapy-induced phlebitis, indicating the effectiveness of these agents in preventing phlebitis.

Legal entity responsible for the study

Kyoto University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

PD-1 inhibitors are breakthrough treatments in many malignancies. Tumour responses are often durable, and some patients experience long term disease control and potentially cure. Patients on long-term treatment may experience chronic toxicity and inconvenience from regular infusions, which may affect quality of life (QoL). Literature on this population is sparse.

Methods

We performed a descriptive study at two hospitals for patients with advanced malignancy currently treated with nivolumab or pembrolizumab monotherapy for ≥6 months. Chronic toxicity (≥4weeks) was graded by CTCAE v4.03. Inconvenience of treatment, and impact of toxicity and inconvenience on QoL were rated on a Likert 4 point scale. QoL was measured by EORTC QLQ-C30.

Results

We recruited 44 patients (mean age 66 years, range 33-87) of ECOG 0-2 treated with pembrolizumab (n = 28) or nivolumab (n = 16) for a median 18 months (range 6-60) in a range of cancers (melanoma, n = 21; non small cell lung, n = 13; renal cell, n = 6; bladder, n = 1; small cell lung, n = 1; endometrial, n = 1; adrenocortical, n = 1). Most patients were partial (n = 30) or complete responders (n = 6). 86% (n = 38) and 39% (n = 17) reported current chronic toxicity of any grade and grade 2 respectively. Common toxicities were itch (52%; n = 23), fatigue (41%; n = 18), rash (32%, n = 14), hypothyroidism (23%, n = 10) and dry mouth (21%, n = 9). Frequent grade 2 toxicities were hypothyroidism (23%, n = 10) and hypophysitis (5%, n = 2). 92% of patients rated the direct impact of toxicity on QoL as “none” (39%) or “very little” (53%). Participants had better functional and symptom outcomes on all QLQ-C30 scales compared to EORTC QLQ-C30 patient reference values. Global QoL was 70.6 compared to the reference value mean of 61.3. Nausea/vomiting, diarrhoea and fatigue were low with mean scores of 3, 6.1 and 20.5 respectively. Cognitive functioning was high at 90.5. Common reasons of inconvenience were schedule rigidity (25%, n = 11), work interference (16%, n = 7) and travel (14%, n = 6).

Conclusions

Most patients able to be on long term PD-1 inhibitors experience grade 1-2 toxicity which have very little or no impact on QoL, and report better QoL than reference values for the general cancer population.

Legal entity responsible for the study

Crown Princess Mary Cancer Centre, Westmead Hospital

Funding

None

Disclosure

M. Carlino: MSC is an advisory board member for MSD, BMS, Novartis, Amgen and Pierre Fabri. H. Gurney: HG is an advisory board member for MSD and BMS. R. Hui: RH has been an advisory board member for: Merck Sharp & Dohme, AstraZeneca, Novartis, Bristol-Myers Squibb, Pfizer Speaker honorarium: Merck Sharp & Dohme, AstraZeneca, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, Roche. All other authors have declared no conflicts of interest.