O-003 - IMM-101 Extends Survival and Maintains Quality of Life in IMAGE 1, a Randomized, Open-label Phase II Trial comparing Gemcitabine with and without IM...

Date 04 July 2015
Event WorldGI 2015
Session Oral and LBA abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Cancer Immunology and Immunotherapy
Pancreatic Cancer
Presenter A. Dalgleish
Citation Annals of Oncology (2015) 26 (suppl_4): 108-116. 10.1093/annonc/mdv235
Authors A. Dalgleish, H. Bilyard, L.R. Brunet
  • St George's University of London, London/UK

Abstract

Introduction

The three most important issues for patients with pancreatic cancer and their caregivers are QoL, extending life and managing symptoms. Although existing treatment options can extend survival, this may be at the expense of QoL. We have reported that IMM-101, a systemic immunomodulator containing heat-killed Mycobacterium obuense (NCTC13365), provides significant survival benefits in this patient population when given in combination with Gemcitabine (Gem). Here, we provide evidence that this combination maintains and may actually improve certain aspects of QoL compared to chemotherapy alone.

Methods

In IMAGE 1, advanced pancreatic cancer patients (WHO score 0-2, n = 110) were assigned randomly to receive IMM-101 (0.1 mL, 10 mg/mL intradermally) + Gem (1000 mg/m2 q7d3) (n = 75) or Gem alone (n = 35) for a 12-cycle maximum. The efficacy endpoint of primary interest was OS. PFS, safety, tolerability and QoL were also assessed. Patients were asked to complete the cancer-specific EORTC QLQ-C30 questionnaire, which includes five functional scales (physical, role, cognitive, emotional, social functioning), three symptom scales (fatigue, pain, nausea), a global health status scale and single items (dyspnoea, appetite loss, constipation, diarrhoea, insomnia, financial impact). A pancreatic cancer-specific questionnaire (QLQ-PAN26, incorporating 12 single items and 5 combined scores) was also completed. Responses were used to compute QoL scores, which were analysed by repeated measures analysis of covariance using least squares (LS) means.

Results

As previously reported, IMM-101 was associated with clinically meaningful increases in OS and PFS, with no additional burden of adverse events above those relating to chemotherapy or the underlying disease. Patients with metastatic disease (n = 92) benefitted the most from combination treatment with a significant 59% increase in median OS from 4.4 months (Gem, n = 28) to 7 months (IMM-101 + Gem, n = 64) (p = 0.01). Results from QoL questionnaires showed that patients receiving IMM-101 + Gem did not suffer deterioration in QoL and clinically meaningful overall improvements in several parameters, as measured by differences in LS means in the two groups, were observed. Compared to patients receiving IMM-101 + Gem, global health and functional scale scores of patients receiving chemotherapy alone deteriorated earlier in the course of the study. The effects on emotional behaviour, such as cognitive, social and emotional functioning, which showed consistent and clinically meaningful improvements, are noteworthy. The sample size and variability in questionnaire completion rates at each time point are limitations to the formal statistical analysis of the results but differences in LS means over time are supportive of a longer time to deterioration in QoL for the IMM-101 + Gem combination.

Conclusion

The significant survival benefits in patients with advanced pancreatic cancer treated with IMM-101 + Gem were not accompanied by deterioration in QoL. Instead, patients reported an improvement in several QoL scores. Extending survival while maintaining or improving QoL and without loss of functional status is an important aspect of treatment for these patients.