Search

12020 Background: Early referral to palliative care was associated with improved health-related quality of life (HRQL) and overall survival (OS) in a US phase 3 trial in lung cancer patients (pts). International studies in mixed cancer types have reported conflicting results. PEARL aimed to determine whether early referral to palliative care would improve HRQL, OS, and resource use in Australian pts with recently diagnosed, advanced thoracic cancers. Methods: Eligible participants (pts) in this unblinded, multi-centre, randomised, phase 3 trial had advanced thoracic cancers diagnosed within 60 days, and the ability to complete patient-rated outcome measures (PROMS). Pts were randomly allocated to early referral to palliative care (ER) or referral at clinician’s discretion (DR). All pts received standard oncological care. PROMS were completed at baseline, every 3-4 weeks for 6 months, then 6-8 weekly. The primary objective was to determine the frequency of sustained, substantial improvements in HRQL, defined as a 5-point improvement in the FACT-L Trial Outcome Index (TOI) maintained for at least 2 consecutive assessments. Secondary outcomes included OS, documentation of advanced care plan (ACP), PROM scores at 12 weeks, anxiety/depression (PROMIS-ED), lung cancer symptoms (FACT-L), global HRQL (ICECAP-SCM), carer-satisfaction and burden, and understanding of illness and prognosis. The accrual target of 200 gave 80% power (alpha 0.05) to detect an absolute improvement of 20% in the proportion of pts achieving the primary endpoint. Results: 113 pts and 78 carers were recruited when the trial closed for slow accrual. Pt characteristics were well balanced: 88 (75%) had NSCLC, 18 (16%) small cell and 7 (6%) mesothelioma. Median age was 69 (IQR 62-74), 63 (56%) were male; systemic anti-cancer therapy ongoing or planned in 88 (78%). Median follow-up was 30 months. First consultations with a palliative care specialist within 60 days of diagnosis occurred in more pts assigned ER vs DR (57% vs 3.5%). Sustained substantial improvements in FACT-L TOI were reported by similar numbers of pts assigned ER vs DR: 33% vs 32%, p = 0.9. OS was similar among those assigned ER versus DR (median 12 vs 18.4 months, p = 0.11). A similar % had a written advanced care plan at death: 15/40 (39%) vs 15/33 (47%). We found no important differences between arms in global HRQL (ICECAP-SCM), depression/anxiety (PROMIS-ED), lung cancer symptoms (FACT-L), carer satisfaction (FAMCARE-2), carer burden (CRA), or understanding of illness by carers or pts. Conclusions: Early referral to palliative care, compared with discretionary referral, did not improve important outcomes for Australian thoracic cancer pts or carers. Our findings suggest that the palliative care needs of such pts were addressed equally well by delayed referral when clinically indicated, resulting in reduced burden for resource-limited specialist palliative services. Clinical trial information: ACTRN12617000166370. more...

12008 Background: The aim of this multi-centre, randomised, double-blinded, placebo-controlled, phase 2/3 trial is to determine efficacy of addition of oral cannabis in adults with any malignancy of any stage, experiencing CINV during moderate-highly emetogenic intravenous chemotherapy, despite guideline-consistent anti-emetic prophylaxis, requiring ≥ 2 chemotherapy cycles. Here we report the crossover phase 2 component results. Methods: Treatment consisted of 1 cycle of oral THC 2.5mg/CBD 2.5mg (TN-TC11M) capsules tds days -1 to 5 and 1 cycle matching placebo in a crossover design, then blinded patient preference for a 3rd cycle. Primary end-point is difference in proportion of patients with ‘complete response’ (no emesis & no use of rescue medications) during 0-120 hours from chemotherapy between cycles. 80 patients provides 80% power with 2p of 0.1 to detect a 20% difference. Results: 81 patients recruited (2016-9). 72 completing 2 cycles are included in efficacy analyses. 78 not withdrawing consent are included in safety analyses. Median age was 55 years (range 29-80), 78% were female, 42% report historic cannabis use, 55% were treated with curative intent. Most common regimens were AC (26%), FOLFOX (17%). All received steroids & 5-HT3 antagonist, 79% received NK-1 antagonist, 4% received olanzapine. Efficacy is shown in table. 83% preferred cannabis to placebo. Most common bothersome cannabinoid-related adverse events (cannabis, placebo) were sedation (19%,4%), dizziness (10%,1%), disorientation (3%,0%). No SAEs were attributed to THC/CBD. Conclusions: Addition of oral THC/CBD to standard anti-emetics was associated with less nausea & vomiting but additional side effects. Most preferred THC/CBD to placebo. Based on these positive results, the definitive parallel phase 3 trial component continues (additional n=170). Acknowledgements: Trial participants, investigators, research staff. Funding from NSW Government Dept of Health. Clinical trial information: ACTRN12616001036404 . [Table: see text] more...

TPS9631 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven remarkably effective in the treatment of advanced EGFR mutant non-small cell lung cancer (NSCLC). However, drug resistance is inevitable and outcomes with subsequent platinum-pemetrexed chemotherapy are poor. The role of immune-checkpoint inhibitor monotherapy in EGFR mutant NSCLC remains uncertain with trials demonstrating inferior survival outcomes compared to chemotherapy. However, a recent randomised study with combination checkpoint inhibitor-chemotherapy demonstrated improved survival over chemotherapy alone in this patient population. This study aims to evaluate the efficacy and tolerability of combination dual immune-checkpoint blockade, durvalumab and tremelimumab, with platinum-pemetrexed chemotherapy in metastatic EGFR mutant NSCLC following progression on EGFR-TKIs. Methods: This international phase II cohort study will recruit 100 participants from Australia and Taiwan with advanced EGFR mutant NSCLC following disease progression with EGFR-TKIs [Cohort 1 (n=50): T790M mutation negative on tissue and plasma; Cohort 2 (n=50): T790M mutation positive on tissue and/or plasma, and progression on3rd generation TKIs]. Participants will receive 4 cycles of induction durvalumab 1500mg and tremelimumab 75mg with platinum-pemetrexed chemotherapy every 3 weeks, followed by maintenance durvalumab 1500mg and pemetrexed 500mg/m2 every 4 weeks until disease progression. Response will be assessed at 6 and 12 weeks, then 8-weekly during the first year, and 12-weekly thereafter. Major endpoints include objective tumour response rate (OTRR; RECIST1.1; primary), disease control rate, OTRR (iRECIST), progression-free survival, overall survival, and adverse events. Correlative studies include biomarker assessment as potential predictive/prognostic factors. ILLUMINATE is a collaboration between the Australasian Lung Cancer Trials Group, National Health Research Institutes (Taiwan) and the NHMRC Clinical Trials Centre, University of Sydney. As of 6/2/2020, 11 of planned 100 participants have been recruited. Clinical trial information: NCT03994393 . more...

TPS10128Background: Up to half of patients receiving chemotherapy of moderate or high emetic risk experience CINV despite optimal anti-emetic prophylaxis. Limited evidence suggests cannabinoid medi... more...