SWOG researchers to present practice-changing research at virtual ASCO 2021

"SWOG always brings an impressive portfolio of work to the ASCO annual meeting," said SWOG Chair Charles D. Blanke, MD, "and this year I'm particularly excited about the research our investigators are presenting because it includes results that are likely to be practice-changing."

Investigators will present 12 abstracts from SWOG-led or co-led studies and 11 abstracts from studies led by other groups within the National Clinical Trials Network (NCTN).

Results from S1216 will be presented orally by study chair Neeraj Agarwal, MD, of the Huntsman Cancer Institute at the University of Utah. S1216 compared androgen deprivation therapy (ADT) combined with TAK-700 to the standard treatment of ADT with bicalutamide in patients who had metastatic hormone-sensitive prostate cancer. The study found that adding TAK-700 to ADT lengthened median progression-free survival in these patients and improved prostate-specific antigen response. The combination did not, however, significantly lengthen median overall survival, though it is worth noting that the median overall survival seen in the control arm was higher than has been reported in other recent phase 3 trials in this setting (abstract 5001).

Kenneth Grossmann, MD, PhD, also of the Huntsman Cancer Institute at the University of Utah, will give an oral presentation of S1404 results. S1404 tested pembrolizumab against therapies that were the standard of care at the start of the trial--either high-dose interferon or ipilimumab--in patients with high-risk resected melanoma. The drug significantly lengthened relapse-free survival in these patients, although it did not provide a statistically significant improvement in overall survival. The safety profile of pembrolizumab was more favorable than that of either ipilimumab or high-dose interferon in this patient population. Notably, the overall outcomes of patients on this trial were substantially better than what was predicted when the study was designed, likely due to the widespread availability of better therapies in the metastatic setting. This is good news for patients with melanoma (abstract 9501).

Here are highlights from some of the other SWOG work to be presented at ASCO 2021.

• A secondary analysis of data from S0809 will be presented by Sepideh Gholami, MD, of the University of California, Davis. Previously reported results from S0809 showed that adjuvant capecitabine and gemcitabine followed by radiation therapy with capecitabine improved overall survival times in patients with resected extrahepatic cholangiocarcinoma and gallbladder cancers compared to historical controls. This secondary analysis asked whether this adjuvant chemoradiation provided a benefit specifically to those patients whose cancers had spread to their lymph nodes. Researchers conclude that this adjuvant therapy combination after surgery improves patient outcomes regardless of whether lymph nodes are involved and can have additional benefit in those with lymph node involvement, perhaps by preventing local recurrence (abstract 4104).
• Long-term results from S1200 will be presented by Dawn L. Hershman, MD, MS, SWOG's vice chair of NCI's Community Oncology Research Program research and a professor of medicine and epidemiology at Columbia University. Many breast cancer patients are treated with drugs called aromatase inhibitors to reduce the chance that their cancer will return. These drugs, however, often cause joint pain, leading many patients to discontinue using them. S1200 tested whether acupuncture could provide pain relief to these patients. The trial compared a true acupuncture procedure to a sham procedure and to wait-list controls. In 2017, early results from S1200 reported better pain outcomes from true acupuncture through 24 weeks after the start of the therapy. Hershman's ASCO 2021 presentation on the 52-week outcomes from the trial echoes those promising early findings. Women with breast cancer and taking aromatase inhibitors who were treated with true acupuncture for 12 weeks for joint symptoms had lower worst pain levels than patients receiving sham acupuncture and wait-list controls. These benefits persisted over one year even though the initial course of acupuncture was only 12 weeks (abstract 12018).
• Davendra Sohal, MD, MPH, of the University of Cincinnati Medical Center, will present a secondary analysis of data from S1505. S1505 enrolled patients with operable pancreatic ductal adenocarcinoma. These patients were randomized to get a course of either neoadjuvant FOLFIRINOX or gemcitabine-nab paclitaxel before surgery. Sohal's analysis looked at the relationship between patients' skeletal muscle and adipose tissue measurements and their overall survival times. The analysis showed that higher visceral fat was associated with lower overall survival among these patients (abstract 4131).
• Results from S1605 will be presented by Peter Black, MD, of the University of British Columbia. S1605 was a phase II trial that tested the efficacy of the drug atezolizumab in patients with non-muscle-invasive bladder cancer that was unresponsive to treatment with bacillus Calmette-Guerin (BCG). Radical cystectomy is the standard of care for these patients, however some patients are not eligible for surgery due to poor general health and some choose to preserve their bladder. The observed rate of response to atezolizumab in S1605 suggests this drug could be a valuable treatment for these patients (abstract 4541).
• An update on the toxicity data for S1800A, one of the sub-studies run as part of the Lung-MAP trial, will be presented by Karen Reckamp, MD, of Cedars-Sinai Medical Center. Lung-MAP is a master protocol for patients with stage-IV non-small cell lung cancer, and those who were not eligible for a biomarker-matched sub-study were enrolled to S1800A. Here they were randomized to either ramucirumab plus pembrolizumab or to an investigator-chosen standard of care treatment. Researchers found that the rate of Grade-3 and higher toxicities was lower in patients in the ramucirumab plus pembrolizumab arm than in patients who received standard of care treatment. Efficacy outcomes are expected in the fall of 2021 (abstract 9075).
• Results from another Lung-MAP sub-study, S1900A, are to be presented by Jonathan W. Riess, MD, a SWOG investigator at the University of California Davis Comprehensive Cancer Center. S1900A was a phase II study of the PARP inhibitor rucaparib in patients with advanced (stage IV) non-small cell lung cancer (NSCLC) whose tumors had at least one of two specific genetic changes (genomic loss of heterozygosity and/or a deleterious BRCA1/2 mutation). Prior studies have found that PARP inhibitors such as rucaparib are robustly effective in treating a range of cancers that display these genomic changes. It was not known, however, if PARP inhibitors were also effective in treating advanced-stage NSCLC with these changes. S1900A was designed to answer this question. The study failed to show sufficient efficacy of rucaparib in these patients in the overall population. The researchers conclude that genomic loss of heterozygosity does not predict sufficient activity of rucaparib in NSCLC. However, in an unplanned analysis, a signal towards preferential clinical activity was observed in patients with NSCLC whose tumor harbored mutations in both alleles of the BRCA gene. Studies following up on this finding are ongoing (abstract 9024).

Studies S1216, S1404, S0809, S1200, S1505, S1605, S1800A, and S1900A are sponsored by the National Cancer Institute, part of the National Institutes of Health, led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN).

S1216 was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, and CA180821 and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company Ltd).

S1404 was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, and CA180863 and in part by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

S0809 was funded by the NIH/NCI through grants CA180888 and CA180819.

S1200 was funded by the NIH/NCI through grants CA189974 and CA37429 and by the NIH Center for Complementary and Integrative Health and the Office of Research on Women's Health AT006376.

S1505 was funded by the NIH/NCI through grants CA180888 and CA180819.

S1605 was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, CA180821, and CA180863 and in part by Roche/Genentech, which supplied atezolizumab and funding.

S1800A was funded by the NIH/NCI through grants CA180888, CA180819, and CA180821; the Foundation for the National Institutes of Health; and in part by Eli Lilly and Company and MSD International GmbH.

S1900A was funded by the NIH/NCI through grants CA180888, CA180819, CA180821, and CA180863; the Foundation for the National Institutes of Health; and in part by Clovis Oncology, Inc.