clinical study insights

Quality of Life as an Outcome in the Treatment of Metastatic Pancreatic Cancer

by Thomas A. Abrams, MD, Andrew Hendifar, MD, MPH, Gauri Varadhachary, MD

Overview

Despite the high mortality rate in metastatic pancreatic cancer, there is optimism surrounding improved outcomes with newly developed treatment regimens. Our featured experts in the field discuss the importance of quality of life as an outcome in the treatment of metastatic pancreatic cancer.

Q:

Is there currently an evidence-based approach to symptom management and quality-of-life improvement in patients with advanced pancreatic cancer?

Expert Commentary

Andrew Hendifar, MD, MPH

Co-Director, Pancreas Oncology
David Geffen School of Medicine
Cedars Sinai Medical Center
Los Angeles, CA

I think this is very important. The evidence-based approach is there for effective symptom management and quality of life, but it just has not been codified. Therefore, if you speak to a pain specialist, gastrointestinal (GI) doctor, or nutritionist, the pain specialist will tell you how to treat pain in an evidence-based manner. The GI doctor will tell you how to approach the layer of obstruction, and the nutritionist will tell you how to approach pancreatic enzyme insufficiency. For the oncologist who has a busy practice and has a lot to handle, it can be a lot to address all of these concerns, and we need to get our palliative care colleagues involved and helping out. For all of the clinical trials that look at combination chemotherapy, even single-agent gemcitabine study vs 5-fluorouracil (5-FU), they all show definite improvement in quality of life, and it is interesting that that aspect of the treatment really has not been emphasized, except for the gemcitabine study, which was in 1997 (a long 20 years ago). That was basically approved for quality-of-life benefit, but the measure of quality of life at that time wouldn’t stand today. Now we have better validated instruments that we need to use for quality of life, which is vital to improving the outcomes in this group. We have to understand more than response rate and overall survival. We have to look at quality of life and how patients are actually doing, and that will really inform how we treat them. For first-line treatment with either gemcitabine + nab-paclitaxel or with FOLFIRINOX*, at first blush you’re likely to wonder if it is really a good idea for an advanced pancreatic patient who is really sick and terminal. You might wonder if you should really do it, and then you look at the quality-of-life data and you realize, not only do they live longer but their quality of life is improved. So most clinicians would feel reassured about aggressive first-line treatment.

*FOLFIRINOX: FOL=leucovorin calcium (folinic acid); F=5-fluorouracil; IRIN=irinotecan hydrochloride; OX=oxaliplatin

“We have to understand more than response rate and overall survival. We have to look at quality of life and how patients are actually doing, and that will really inform how we treat them.”

Andrew Hendifar, MD, MPH

Thomas A. Abrams, MD

Assistant Professor of Medicine
Harvard Medical School
Senior Physician
Dana-Farber Cancer Institute
Boston, MA

I think that we do tend to separate quality of life and overall survival as 2 separate outcomes. Of course you can measure them differently, but in reality, they dovetail. With good quality of life, patients are going to live longer. By combining quality of life and overall survival as outcomes, we will have better uptake in the community as a very important way of assessing patients and seeing how they’re responding to treatment. There have been several landmark studies in pancreatic cancer that used validated quality-of-life measures and have shown consistently that the application of cytotoxic chemotherapy along with very good supportive care will prevent the degradation of quality of life in patients with this disease. So, I think there are certainly several validated systems for measuring symptom burden and quality of life, and we’ve incorporated them into some landmark studies and found that quality of life can certainly be preserved for patients who are receiving chemotherapy and having their symptoms managed aggressively through supportive measures.

“There have been several landmark studies in pancreatic cancer that used validated quality-of-life measures and have shown consistently that the application of cytotoxic chemotherapy along with very good supportive care will prevent the degradation of quality of life in patients with this disease.”

Thomas A. Abrams, MD

Gauri Varadhachary, MD

Professor and Medical Director, Gastrointestinal Center
University of Texas MD Anderson Cancer Center
Department of Gastrointestinal Medical Oncology
Houston, TX

I agree. The only thing that I would add is that there are validated tools, but we need to do better with patient-reported outcomes. That is key, and functional interference is really important. For one patient, grade 2 fatigue could mean sitting on the couch all day, and for another patient grade 2 fatigue could mean managing their work, coming home, finishing homework with their kids, getting done with all the chores, and it’s still grade 2 fatigue. The question is: how validated are the tools that they’re using today? What does it mean for the patients and their outcomes and their functional interference for their day-to-day life? I am hopeful that we do better. Clearly, as therapies improve and patients live longer based on new therapies that work, their quality of life will improve, but we need to get that functional interference part right.

References

Janda M, Neale RE, Klein K, et al. Anxiety, depression and quality of life in people with pancreatic cancer and their carers. Pancreatology. 2017;17(2):321-327.

Laquente B, Calsina-Berna A, Carmona-Bayonas A, Jiménez-Fonseca P, Peiró I, Carrato A. Supportive care in pancreatic ductal adenocarcinoma. Clin Transl Oncol. June 13, 2017. doi: 10.1007/s12094-017-1682-6. [Epub ahead of print].

Okada KI, Shimokawa T, Hirono S, et al. Effect of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival in patients with borderline resectable pancreatic cancer: a prospective multicenter phase II trial (NAC-GA Trial). Oncology. July 19, 2017. doi: 10.1159/000478660. [Epub ahead of print].

Pelzer U, Blanc JF, Melisi D, Cubillo A, Von Hoff DD, Wang-Gillam A, et al. Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis. Br J Cancer. 2017;116(10):1247-1253.

Picozzi V, Narayanan S, Henry Hu X, Vacirca J. Health-related quality of life in patients with metastatic pancreatic cancer. J Gastrointest Cancer. 2017;48(1):103-109.

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