So my study was focussed on patients with metastatic pancreatic cancer who are older and vulnerable. Those were patients over the age of 70 with ECOG performance status 0-2, but they also had to have some other vulnerability – either decreased function, increased comorbidities, issues with cognition or, if they were over the age of 80, they also qualified for this trial. And then this group of patients were randomised between one of two treatment arms – these were dose-reduced chemotherapy regimens that included either gemcitabine and nab-paclitaxel given every other week or 5FU and liposomal irinotecan at a dose reduction of the liposomal irinotecan. Patients were treated until their disease progressed and we followed them for survival on the trial. That was the study.

What was the study design?

In addition to evaluating the toxicity and the efficacy of these regimens, every patient underwent a complete geriatric assessment at baseline and then had repeated geriatric assessment at three and at six months. The idea, in addition to understanding the outcomes and the efficacy of the regimen, we also wanted to understand if there were specific geriatric factors that contributed to these outcomes and maybe would help us really identify patients that are candidates for therapy.

I should also add that we collected a lot of additional information about these patients, including quality of life measures as well as some biomarkers of aging and understanding of sarcopenia through CT scans. Those are analyses that are still ongoing.

What were the results?

So the results, first of all, showed that in this very vulnerable patient population we had a significant number of patients that were unable to initiate therapy or receive more than one cycle of treatment. So that really highlighted how sick these patients are and how challenging it is to treat these patients.

In terms of outcomes, what we noticed is that there was really no significant difference between the two treatment arms, the outcomes were the same, but they were overall quite poor with an overall survival of somewhere around five months if we looked at the intent to treat population. We did a separate analysis that looked specifically at patients that received more than two doses of the treatment, so basically more than one month of therapy, and in this group of patients the median overall survival was eight months. That actually is in line with what we see with the full chemotherapy regimens for metastatic pancreatic cancer. That actually highlights the fact that there are probably a subset of these vulnerable patients that could benefit from chemotherapy versus patients who are really too frail and maybe the right thing to do is not give them chemotherapy but do more supportive care measures.

In the Society of Geriatric Oncology meeting I presented some of the analyses that were done looking at the geriatric assessment factors that were collected at baseline. We saw that there was a clear difference between patients who came in with a good performance status of 0-1 versus those with ECOG performance status of 2. Clearly patients with a very poor performance status did very poorly with a very poor overall survival that questions the benefit of this chemotherapy.

We did a more in-depth analysis looking at the correlation between geriatric factors at baseline and survival and what we found is that three factors really stood out in terms of their correlation with survival and that was instrumental activities of daily living – so patients that had issues with function in that category faired much worse; nutrition, that was evaluated by the Mini Nutritional Assessment, and that is clearly correlated so patients that had nutritional issues fared much worse and had a worse overall survival. Then the last one was depression – patients that were depressed by the geriatric depression scale had much worse overall survival compared to patients that had lower depression scores on that scale. All of these three areas came out with strong association in the univariate and a multivariate analysis.

In addition, we looked at the quality of life measured, We used the FACT-Hep questionnaire to evaluate quality of life and FACT-Hep has various scales built in to this assessment. Every single one of these tools correlated strongly with survival. So the patients’ quality of life at baseline, if they had poor quality of life, and that entails both physically, emotionally, in terms of social and psychological support, all of those factors, every single one of them correlated with survival and poor quality of life at baseline correlated with much lower survival from this treatment.

Then finally the last part was toxicity. We looked at toxicity of these two regimens. Overall the rates of grade 3-5 toxicities were very similar between the two regimens. There are different types of toxicities with each of these drugs which gives physicians the option of deciding which regimen would fit best for the patient. So, for example, with 5FU and liposomal irinotecan we see more diarrhoea, so maybe there are patients where diarrhoea is not a toxicity that they would tolerate and you would recommend doing gemcitabine and nab-paclitaxel instead. With gemcitabine and nab-paclitaxel we saw more neuropathy and maybe that’s an issue that you would want to avoid in certain patients and you would not pick this regimen. So, from a toxicity perspective, there’s really no significant difference between the two arms.

How tolerable is gemcitabine/nab-paclitaxel to 5 fluorouracil/leucovorin/liposomal irinotecan in older patients?

In my opinion the main take-home message from this trial is that in this vulnerable patient population we really need to think about the benefit we get from chemotherapy. It’s not one size fits all, we can’t expect everybody to have the same benefit from chemotherapy and we really need to figure out a way to identify the patients that could benefit from it. So understanding these baseline factors could potentially help us a) identify patients that could benefit, and b) provide supportive care measures at baseline that potentially can improve outcome.

The other piece is that the outcomes are quite poor in this patient population and this really raises the question of is it beneficial to give vulnerable older adults with metastatic pancreatic cancer chemotherapy? Should these patients be offered best supportive care? So the data provides oncologists with evidence-based information to have a shared decision making with their patients and understand if treatment is worthwhile or not.

I talked about the clinical significance but one more thing that I would like to add is that the results clearly show that geriatric assessment can identify factors that we don’t identify in routine clinical assessment. You really need to have a comprehensive evaluation of the patient before they start chemotherapy to understand what are the factors that are affecting their ability to tolerate treatment and intervene to try and help them. So whether it is a functional issue and they would require more support at home, physical therapy, whether it’s a nutritional issue that they could benefit from a nutritionist evaluation or some other at home support with nutrition, or whether it’s a cognitive issue that really raises the question of how they can benefit or tolerate therapy, you need to know these things before you’re recommending chemotherapy for this particular disease.

I’ll just add one more comment about another significant that I see in this trial is that this is the first study to be done in older patients with metastatic pancreatic cancer and it really highlights the importance of doing these trials, of understanding the benefit of how we’re treating these patients and understanding that these patients have different needs and different outcomes compared to the general patient population with this disease. I hope this demonstrates the fact that these elderly-specific trials can be done and are feasible. I hope that this opens up the door for future studies in this very prevalent and vulnerable patient population.

What is next for this study?

It’s hard for me to say what’s the next study at this point. I do have some thoughts about other regimens that we can test in the older patient population, maybe looking at treatment regimens in the earlier setting of pancreatic cancer. But before that, we have so much data within this study that we have to weave through, complete all our secondary analyses of looking at the geriatric assessments and how they can help us identify patients for treatment. I’m hoping we can potentially come up with even maybe a nomogram that helps us calculate the risks that patients have with chemotherapy or the benefit they would get from chemotherapy based on our results. And then get analysis of the biomarkers and of the sarcopenia analysis, all the not clinical but maybe biological factors that could help provide more information to help us guide patient selection and patient treatment. So I’m really excited to continue with these analyses and report the results.