Our members publish SWOG research findings in a journal or present them at a professional meeting at a rate of more than three times per week, on average – too frequently for me to be able to highlight any kind of significant fraction of them in this column.

Typically, I reserve my coverage in this space for the primary results of big trials. This week we have primary results from two such studies – S1416 in breast cancer and S1815 in biliary tract cancers.

S1416: Extending the use of PARP inhibitors?
PARP inhibitors have been shown to be effective in treating breast cancers in patients who have germline mutations in the BRCA1 or BRCA2 gene. S1416, led by Eve Rodler, MD, with Priyanka Sharma, MD, as translational medicine co-chair, has for the first time reported a benefit from a PARP inhibitor in patients with breast cancer who do not have a germline BRCA1/2 mutation but whose tumors have other changes that similarly affect the DNA repair abilities of cells.

Roughly 40 to 50 percent of triple-negative breast cancers exhibit this “BRCA-like” phenotype, and the S1416 team asked whether a PARP inhibitor could also be effective in treating these BRCA-like breast cancers.

Investigators randomized 320 patients with metastatic breast cancer to receive cisplatin chemotherapy with or without the PARP inhibitor veliparib. All patients were prospectively assigned, based on blood and tumor tissue testing, to one of three distinct groups describing their type of cancer: BRCA-mutated, BRCA-like, or non-BRCA-like breast cancer.

Among patients with BRCA-like breast cancer, those on the veliparib arm had significantly longer median progression-free survival than those on the control arm: 5.9 versus 4.2 months. They also had numerically better median overall survival and objective response rates, though those differences did not reach the level of statistical significance.

The S1416 results suggest the possibility of expanding the use of PARP inhibitors to treat breast cancer beyond only cancers with germline BRCA1/2 mutations.

The findings were published recently in Lancet Oncology.

S1815: First randomized US phase III in biliary tract cancers
Biliary tract cancers are a group of rare malignancies that include gall bladder cancer and cholangiocarcinoma. SWOG’s S1815 was the first randomized phase III trial in the US in these cancers. Study chair Dr. Rachna Shroff reported the results in an oral presentation at the recent 2023 ASCO GI Symposium.

The study was designed based on promising improvements in median progression-free survival and overall survival times in an earlier phase II trial that added nab-paclitaxel to the standard gemcitabine plus cisplatin regimen. 

In the phase III S1815, 441 patients with advanced biliary tract cancers were randomized to gemcitabine plus cisplatin with or without the addition of nab-paclitaxel. But the promising results seen in the smaller phase II trial were not confirmed in this phase III: although median overall survival time on the nab-paclitaxel arm was slightly longer than that on the control arm (14 versus 12.7 months), the difference was not statistically significant.

So, S1815 was considered a negative trial, but we learn from every trial we conduct, and we have two notable positives to report from these results.

First, subset analyses showed that patients who had locally advanced disease and those who had gallbladder carcinoma did have significantly longer overall survival times than corresponding patients on the control arm, so there may be benefit in exploring this regimen further for certain groups of patients. 

The second positive is that this clinical trial in a group of rare cancers randomized 441 eligible patients in just over two years, with more than 150 sites nationwide enrolling at least one patient. Anyone who doubts the benefits of the reach and depth of the NCTN and NCORP networks should pay attention to those results.

 

On a different note, I am saddened to report that Dr. Roy Decker, chair of SWOG’s radiation oncology committee since 2019, died this past weekend at his home.

Dr. Decker was professor of therapeutic radiology at Yale University and led their Stereotactic Body Radiotherapy Program. His friend and colleague at Yale Dr. Roy Herbst described him simply and eloquently – “a great doctor and an even better friend.” He was a major force in SWOG.

Dr. Decker’s family have said they will hold a celebration of life for close friends and family in March, and there will be a later occasion for his many colleagues and others who wish to pay their respects. They invite friends to leave memories or tributes on the family’s CaringBridge site.

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Mar 8, 2024
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