Treatment for metastatic pancreatic cancer has seen progress in recent years, but outcomes remain poor and treatment advances that can prolong patients’ lives, even for a few months, are eagerly awaited. Two papers published today in the scientific journal Nature Medicine report that a new combination of two drugs that are FDA-approved for other conditions may significantly delay progression of pancreatic cancer in cells and in mice. Furthermore, the first patient treated with this combination experienced a prolonged response that lasted almost 6 months.
In light of these promising results, Cancer Commons is partnering with xCures to track the experiences of patients who choose to try this new combination therapy.
Most pancreatic cancers have a mutation in a gene called KRAS. Mutated KRAS activates and signals other proteins to drive cancer progression. Creating a drug to inhibit KRAS itself has proven to be very difficult, so most efforts to inhibit KRAS have focused instead on proteins that are activated by KRAS, of which MEK and ERK are two that are easier drug targets. However, MEK inhibitors have little activity in KRAS-mutant cancers, and while ERK inhibitors are in clinical trials for KRAS-mutant cancers, they don’t have a deep or lasting effect on their own. Hence, a combination approach may achieve a greater effect in pancreatic cancer.
Many KRAS-driven cancers depend on autophagy, a “recycling” process by which cells break down damaged organelles and macromolecules, and then can reuse their building blocks to maintain themselves. Hydroxychloroquine (HCQ) is an old FDA-approved drug used to treat malaria, and it inhibits autophagy. Based on this discovery and the drug’s availability, HCQ was tested in clinical trials for pancreatic cancer, but it did not have an impact when used alone.
Today’s new publications report that inhibition of MEK or ERK with targeted drugs surprisingly increases autophagy. When the authors of one of the studies tried combining HCQ with MEK or ERK inhibitors, they saw a much stronger inhibition of cancer grown in cells and in tumor-bearing mice.
Based on these compelling pre-clinical data, after fully informed consent and following institutional policies, the investigators began treatment with HCQ and the MEK inhibitor trametinib in a single male patient who had exhausted other treatment options. They were elated to see a rapid response, with 50% reduction in tumor burden as seen on scans, and a profound drop in the tumor marker CA 19-9. The dramatic response, accompanied by a reduction in pain level, lasted for several months before resistance emerged. It is unknown whether this combination will be effective in other patients with advanced pancreatic (or other solid) cancer, but it must be tested.
This is an exciting advancement with two already-approved drugs, which provides patients and their physicians with the opportunity to try this combination “off label” if another proven option is not available. There may be challenges with the cost and insurance coverage, but working with your physician and the pharmaceutical company assistance programs may result in access to treatment.
Cancer Commons always favors participation in clinical trials when possible. Currently, this drug combination is only available in one small clinical trial at the University of Utah. If access to this ongoing clinical trial and/or other standard-of-care treatments is unsuccessful, the compassionate use of this combination may be an option for patients and physicians to discuss.
If you and your physician are contemplating treatment with this combination therapy, please consider being part of our observational study in partnership with xCures. As part of our tracking study, patients can share their experiences and learn from the experiences of others regarding dosing, timing, and strategies for overcoming resistance. If a better treatment comes along, you’ll be the first to know!
To register, click here and benefit from the experience of all patients by collectively exploring this promising development.
For more information, contact us at info@cancercommons.org.
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Cancer Commons is a nonprofit collaborative of patients, physicians, and scientists, dedicated to improving patient outcomes by tightly coupling clinical research and care. We arm patients and their physicians with the knowledge they need to achieve the best possible outcomes, help them access the relevant treatments and trials, and track their results to continuously learn. Visit cancercommons.org for more information.
xCures is developing an AI-based methodology and platform to run ‘Virtual Trials’, which continuously learn from the clinical experiences of all patients, on all treatments, all the time. Each patient’s treatment regimen is adaptively planned by a ‘Virtual Tumor Board’ to optimize their individual outcome, and these plans are coordinated across the whole patient population to maximize collective learning. Visit xcures.com for more information.
