Sue S. Yom, MD, PhD, on Oropharyngeal Cancer and the Feasibility of a Cell-Free DNA Plasma Assay
2022 ASCO Annual Meeting
Sue S. Yom, MD, PhD, of the University of California, San Francisco, discusses a translational analysis from the NRG-HN002 study. This phase II trial established the feasibility of the tumor tissue–modified viral (TTMV) human papillomavirus DNA assay in clinical trial specimens. The goal is to use such an assay to measure tumor volume, levels of TTMV over the course of treatment, and the association of TTMV to treatment outcomes (Abstract 6006).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
At this meeting, we were pleased to present a translational analysis from NRG Oncology. NRG Oncology is a cooperative group that ran a study called NRG-HN002. This was a study looking for a de-intensification arm for HPV positive oropharyngeal cancer patients to take forward into a phase three setting in HN002. We had two arms on the study, which were a chemo radiation arm to 60 gray with weekly cisplatin, as well as an IMRT alone arm that's delivered over five weeks. This translational study was a study of blood specimens that were taking at three pre-specified endpoints. Baseline prior to treatment, after two weeks of radiation therapy or chemo radiation delivery, and then at two to four weeks after the end of the treatment and the participation rates were actually quite good, even though it was a separate substudy. We had about 50% participation over the course of the study, maybe weighing to about 40% by the end of the study. But half of patients donated specimens and we were able to find a few things with three different hypotheses. First of all, at the pre-treatment baseline, we found that there was a weak to moderate correlation of the detection level of the HPV-DNA fragments, which our tumor tissue modified. A little bit more specific than regular cell-free DNA. We were able to find a weak to moderate correlation with the overall gross tumor burden. We also found that 10% of patients were undetectable at baseline for a variety of potential reasons, which were continued to explore, could be mismatch with true HPV mismatched to P16, could be characteristics of the samples which were collected in a national study, could be characteristics of the infection, whether integrated or not. We'll continue to investigate that. For the intro treatment sample at two weeks, after two weeks of treatment, we did find a variation in changes over the course of the study in patients. There was some heterogeneity in the pattern of DNA response, which was interesting to see, although the vast majority of patients ended up at undetectability by the completion of treatment at the post-treatment final time point, but it was interesting to see that variation and also to see that it wasn't necessarily true of all patients that they had continuous decreases in the fragments per ml. Although if you looked at the median level overall, the trend was downward throughout the course of treatment. And then at the post-treatment time point, what we found was that essentially there seemed to be an association that was statistically significant with PFS events, and that is pretty notable because the patients on this study generally did pretty well. And we had a relatively small number of PFS events, but they were associated with continued detectability by the end of treatment. I think what's important about this study on an operational and sort of national scale is that this was done in a large scale national study within the cooperative group setting. And so it really shows the feasibility of being able to conduct meaningful translational research within that setting. And also it gives us a pathway forward. We have been able to confirm with this study that the level of tumor tissue modified HPV-DNA is appearing to be prognostic for outcome. And the fact that we're able to do in this study moves us towards the ability to standardize and possibly do more meaningful research in the future that moves us towards not just prognostic, but predictive biomarker status and potential implementation and actionability. I want to thank all the patients and investigators who cooperated in this study, it was a great team effort. And thank NRG headquarters, especially operations, biospecimen resource and statistical group for their support.
Shilpa Gupta, MD, of the Cleveland Clinic Foundation, discusses an updated consensus definition for standard therapy and clinical trial eligibility for patients with metastatic urothelial cancer who are platinum-ineligible, criteria that are proposed to guide treatment recommendations for this population. This may be especially important now that the U.S. Food and Drug Administration has restricted the use of first-line pembrolizumab to those who are considered platinum-ineligible (Abstract 4577).
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, The University of Sydney, discusses findings from the NeoTrio trial on neoadjuvant pembrolizumab alone, in sequence with, or concurrent with dabrafenib plus trametinib in patients with resectable BRAF-mutant stage III melanoma. The study may help clinicians determine the optimal combination of therapy (Abstract 9503).
Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Jeanne Tie, MBChB, MD, of Peter MacCallum Cancer Centre, discuss results from the DYNAMIC trial, in which a circulating tumor DNA (ctDNA)-guided approach reduced the use of adjuvant chemotherapy without compromising recurrence-free survival in patients with stage II colon cancer (Abstract LBA100).
Apar Kishor Ganti, MD, of the University of Nebraska Medical Center, discusses results from the CALGB 30610 study, which showed a similar clinical benefit for once- and twice-daily radiotherapy administered to patients with limited-stage small cell lung cancer. While both regimens were well tolerated, patients who received radiotherapy once daily had better quality-of-life scores at week 3 and slightly worse scores at week 12. Patients believed the once-daily regimen was more convenient (Abstract 8504).
Akihiro Ohba, MD, of Japan’s National Cancer Center Hospital, discusses phase II data from the HERB trial on fam-trastuzumab deruxtecan-nxki, which showed activity in patients with HER2-expressing unresectable or recurrent biliary tract cancer (Abstract 4006).