A Systemic Immunomodulator IMM-101 Extends Survival and Maintains Quality of Life in the IMAGE1 Study

The results of a randomised, open-label phase II trial comparing gemcitabine with and without IMM-101 in advanced pancreatic cancer

The survival benefits in patients with advanced pancreatic cancer treated with a systemic immunomodulator, IMM‑101 plus gemcitabine in a randomised, open-label phase II IMAGE1 trial were accompanied by an improvement in several quality of life (QoL) scores. The QoL results were reported at the ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain (1-4 July, 2015). The authors are study investigators from the St George's University of London, London, UK and Immodulon Therapeutics Ltd, London, UK. 

The three most important issues for patients with pancreatic cancer and their caregivers are QoL, extending life and managing symptoms. Although existing treatment options could extend survival, this may be at the expense of QoL. 

The IMAGE1 study team has reported that IMM-101, a systemic immunomodulator containing heat-killed Mycobacterium obuense, provides significant survival benefits in this patient population when given in combination with gemcitabine. These results were presented at ASCO 2015 and at the ESMO World GI Congress in Barcelona, the research team provided evidence that the study combination maintains and may actually improve certain aspects of QoL compared to chemotherapy alone. 

In IMAGE 1, patients with advanced pancreatic cancer and WHO performance score 0-2 (n = 110) were assigned randomly to receive IMM-101 intradermally plus gemcitabine (n = 75) or gemcitabine alone (n = 35) for a 12-cycle maximum.

The efficacy endpoint of primary interest was overall survival (OS). The progression-free survival (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. 

As previously reported at ASCO 2015, 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 (gemcitabine, n=28) to 7 months (IMM-101 plus gemcitabine, n=64) (p=0.01).

Results from QoL questionnaires showed that patients receiving IMM-101 plus gemcitabine did not suffer from 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 plus gemcitabine, 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 plus gemcitabine combination.

The authors concluded that significant survival benefits in patients with advanced pancreatic cancer treated with IMM‑101 plus gemcitabine 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.