The Pancreatic Standard of Care is No Longer So Standard

NIH Clinical Center; Flickr

When doctors diagnose patients with pancreatic cancer, how do they decide which therapy to pursue? Are there standard protocols or guidelines that every doctor follows?

Yes and no.

For many diseases, including cancer, an expert panel of doctors gets together to agree upon drugs and therapies that should be used to treat the illness, based on a systematic review of the medical literature. This “standard of care” is then widely used by healthcare professionals as clinical practice guideline recommendations.

For many years, the standard of care in pancreatic cancer has been:

• Surgery, followed by adjuvant therapy (additional treatment applied after the initial approach, usually chemotherapy or chemotherapy with radiation) for early-stage patients who are in good health, with accessible, ‘resectable’ tumors (tumors that are surgically removable).
• For more advanced metastatic pancreatic cancer, which the majority of patients face, chemotherapy was usually the first treatment given (often referred to as ‘first-line treatment’). For those who are fit enough, the two most common chemotherapy regimens are: FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel (Gemzar plus Abraxane).
• For those who might not tolerate an aggressive chemotherapy treatment, a single drug (gemcitabine) treatment is recommended.
• If the first-line treatment fails, or stops providing benefit as the cancer evolves, the next line of therapy (‘second-line treatment’) is usually whichever regimen was not administered first.

But as the understanding of the biology of pancreatic cancer rapidly evolves, and genetic testing becomes more accessible, treatments have become more and more tailored to each individual patient.

Going Beyond

In some ways, pancreatic cancer treatments have always been customized to each patient. Upon diagnosis, patients undergo evaluations of their general health to determine their ‘performance status,’ or how well they will be able to tolerate certain treatments. Many patients with advanced disease may be suffering from appetite or weight loss, for instance, and may not do well on a treatment that may cause vomiting and diarrhea.

The era of precision medicine has made it possible to personalize treatments based on molecular analysis of individual tumors. In some cases, it may even be possible to target a patient’s specific genetic mutations.

A host of new targeted therapies now exist to treat pancreatic cancer based on these mutations. Erlotinib, for example, is a targeted oral agent in advanced pancreatic cancer.  PARP inhibitors are being explored for those with BRCA1/2 mutations.

Immunotherapy has also been a hot topic in oncology, and it is being explored in pancreatic cancer, with mixed results. Only a very specific patient population has seen significant benefit from immunotherapy so far—those with tumors that have microsatellite instability (MSI-High) or tumors with impaired DNA mismatch repair (MMR-deficient).

The reality is that pancreatic cancer develops many mechanisms to resist the drugs commonly used to kill it, such as aberrant gene expression, mutations, deregulation of key signaling pathways, support of stroma cells, and presence of highly resistant stem cells. This produces an environment that hinders drug penetration, expels the drug from tumor cells, and overcomes the toxic effects of chemotherapy. New treatments may be tried in order to overcome this, and many clinical trials are in place to determine the best solutions.

In fact, the incorporation of clinical trials has become increasingly standard in the care of most patients at some point in their treatment journey.

The New Standard

The medical bodies that develop standards of care have barely been able to keep up with the speed of progress in research and treatment.

The clinical practice guidelines from the American Society of Clinical Oncology (ASCO), for instance, were last updated in 2016, and the European standard set by the European Society for Medical Oncology (ESMO) was published in 2015, although new information is occasionally added to their site.

The most recent guidelines were published by the National Comprehensive Cancer Network in 2021. Outlined in a handy, comprehensive patient guide, the NCCN drops the phrase “standard of care” in favor of “preferred options.” The sheer size of the document (86 pages) is indicative of just how much the treatment field has grown in the past decade. Supportive and palliative care are also given prominent coverage.

What is the new standard of care? Genetics-based tailored treatment and clinical trials that put patients at the cutting edge of therapy. In addition to all the therapies mentioned earlier, there are also off-label treatments, which may be effective against the disease but are not specifically approved to treat pancreatic cancer.

If your doctor has not suggested genetic testing of your tumor, or discussed clinical trial participation, you may wish to ask questions to ensure you are presented with all available options, when making every treatment decision.