Advancing Care Guidelines, One Trial at a Time

The definitive work counting this second item is a 2019 article in JAMA Network Open whose lead author was our biostatistician and health services researcher Joseph Unger, PhD. The senior author was a well-known weekly blogger.

“Association of National Cancer Institute-Sponsored Clinical Trial Network Group Studies with Guideline Care and New Drug Indications” identifies 82 SWOG-led or co-led phase 3 treatment trials, with publication dates going back to 1980, that have been “practice influential,” meaning their results have been included as evidence in clinical care guidelines – specifically the National Comprehensive Cancer Network (NCCN) clinical practice guidelines – or they have been cited in support of US Food and Drug Administration (FDA) new indications.

Practice influential is a little more inclusive than practice changing, and the list of 82 trials includes quite a few studies with negative results. Some of these 82 changed the standard of care, while others affirmed it.

In the five years since that article came out, we’ve continued to publish clinical trial results that have had an impact.

We have also had results which led to  a variety of different types of regulatory approvals. For example:

• S0777 results led to a 2019 approval by the FDA’s counterpart across the pond, the European Medical Association, for the use of a bortezomib, lenalidomide, and dexamethasone combination in patients with myeloma who are not candidates for a transplant.
• S1800A led to a 2022 “breakthrough therapy” designation by the FDA for a pembrolizumab + ramucirumab combination in patients with advanced non-small cell lung cancer.  
• Secondary analysis of S0226 biospecimens helped lead to the FDA’s certification of a new molecular diagnostic assay – the DiviTum TKa test.

Our results also continue to make their mark on care guidelines. In a by-no-means-exhaustive listicle, here are 10 SWOG trials whose results have, since publication of the Unger article, made their way into the NCCN clinical care guidelines.

• S0230, the POEMS trial, which showed that goserelin can protect ovaries from the effects of chemotherapy and thereby help preserve fertility, is cited in the NCCN breast cancer treatment guidelines.
• S0337 found a benefit from intravesical gemcitabine immediately after bladder resection, and its results are among the evidence supporting this as standard practice in the guidelines for non-muscle invasive bladder cancer.
• S1001, in patients with diffuse large B-cell lymphoma, showed that most who have a clear PET scan after R-CHOP therapy can skip subsequent radiation therapy, results that are cited in the presentation of first-line therapies in the guidelines for this disease.
• S1007 RxPONDER’s results are referred to multiple times in the breast cancer guidelines’ discussion of “gene expression assays for consideration of adjuvant systemic therapy.” 
• S1011 … okay, the results of this trial are not yet in the NCCN guidelines, but the trial itself is discussed there as “not yet reported,” and I’m confident the results will be cited there soon (here’s the ASCO 2023 version), supporting standard lymphadenectomy (rather than extended) as the new standard of care with radical cystectomy for muscle-invasive bladder cancer.
• S1500, PAPMET, (whose final overall survival analysis was just published in the Journal of Clinical Oncology) is cited as evidence supporting cabozantinib as a preferred regimen for non-clear cell renal cell carcinoma.
• S1505, which compared two neoadjuvant chemo regimens in early-stage pancreatic cancer and found that patients had similar outcomes on both, is among evidence supporting the review panel’s decision not to recommend specific neoadjuvant regimens at this time (results can also make their mark by reaffirming the standard of care).
• S1609 DART’s immunotherapy combination of ipilimumab and nivolumab has been added to the NCCN guidelines as a treatment option for high-grade neuroendocrine tumors. DART’s results in angiosarcoma have also made it in, indicated as a subsequent line of therapy for advanced disease for certain soft tissue sarcoma subtypes.
• S1801, which showed that starting immunotherapy before surgery versus after it extended event-free survival in patients with resectable stage III-IV melanoma, figures prominently in the discussion of the principles of neoadjuvant therapy in the cutaneous melanoma guidelines.
• S1826’s results have already made their way into the NCCN guidelines for advanced Hodgkin lymphoma, as a new primary treatment option pathway for stage III-IV disease in adults 60 or younger.

Numerous other SWOG results from the last five years are also cited in care guidelines – NCCN’s, ASCO’s, ESMO’s, and others. I like to keep you informed of results most likely to make a mark as our investigators present or publish them. So stay tuned – I’m pretty sure I’ll have more of those to report soon.