Advertisement


Narjust Florez, MD, and Filippo Gustavo Dall’Olio, MD, on NSCLC: New Findings on Tumor Fraction, Durvalumab, and Survival

2023 ASCO Annual Meeting

Advertisement

Narjust Florez, MD, of Dana-Farber Cancer Institute, and Filippo Gustavo Dall’Olio, MD, of Institut Gustave Roussy, discuss circulating tumor DNA tumor fraction, and its link to survival in patients with advanced non–small cell lung cancer (NSCLC) treated with maintenance durvalumab in the UNICANCER SAFIR02-Lung/IFCT1301 trial. Tumor fraction was positive in 16% of patients randomly assigned to receive durvalumab in the study. This population seems to have a limited benefit from maintenance durvalumab after induction chemotherapy (Abstract 2516).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Narjust Florez, MD: In a quick one minute, can you tell us the design of the study? Filippo Gustavo Dall'Olio, MD: Yeah. So basically, SAFIR02 was a randomized phase II trial and the issue they addressed was if immunotherapy anticipated respect to progression, so in a maintenance treatment, could add something respect to the standard of care that was chemotherapy and then maybe pemetrexed in no squamous histology. So, the study was negative. So basically, the patients were randomized two-to-one ratio between durvalumab and standard of care, no difference. And then a subpopulation that was the PD-L1-positive, they found a small difference, but the study was not powered enough to validate it. So we took the samples taken at randomization and we analyze it with the whole genome sequencing with a very low coverage actually, it was 0.1x to calculate the tumor fraction. And this is where the study starts, with the tumor fraction. Tumor fraction is basically is the proportion of ctDNA, of tumor DNA, on the total cell-free DNA. We all have a lot of DNA in blood, but just a part of this DNA is from cancer in patient with tumor, of course. And so we use [inaudible 00:01:38]-based method, so cancer as [inaudible 00:01:41] number alterations, and this allow us to discriminate between normal cell-free DNA and tumor DNA. So these patients were in response or stability of disease because of the design of the study, and so at the beginning we were not sure to find any DNA. But actually 20% of patients were DNA-positive. And so even if they had a radiological response, they still have the disease that was active, and these patients had no benefit from any therapy, actually. So, they are really a population with an unmet need. Narjust Florez, MD: So in these case, are patients that still have circulating tumor DNA and then you try to understand the benefit or the lack of benefit and the tumor fraction is the proportion of these cancer cells circulating after definite treatment? Is that correct? Filippo Gustavo Dall'Olio, MD: Exactly. Exactly. Narjust Florez, MD: That's a very noble use of circulating tumor DNA and I will have to say. So, as we are learning from this study and we want to try to apply in reality, could it be used when we used in some of these commercial platforms outside of the study? Filippo Gustavo Dall'Olio, MD: Yeah, there are commercial platform that calculates tumor fraction, Foundation Medicine, for example. And yeah, there are studies on its use. We have a study with one of these platform, and showing that if you have a high tumor fraction, you don't benefit from immunotherapy in first-line setting and it's better if you add chemo. So, yes, I think it's a part of the future of precision medicine anyway. In escalating treatment, it's very, very nice. We also found that there is quite a strong correlation with tumor burden. We also know that tumor burden is important in addressing the prognosis of patients, but it's not that immediate to incorporate in, for example, in stratification of patient in clinical trials. Because you have to account for sometimes a lot of metastases, so it's not easy for a radiologist to calculate maybe 20, 25 metastases while with a tumor fraction you just have one number, very easy, very immediately, you can use everywhere. Narjust Florez, MD: My last question is, was there any relation with PD-L1 and tumor fraction in these patients? Filippo Gustavo Dall'Olio, MD: No, there was no relationship. And so it's really independent from other biomarkers. Narjust Florez, MD: And to finalize the conversation, how would you summarize the results to the community oncologists that are caring for many of our patients, not only in the US, but all across the globe? Filippo Gustavo Dall'Olio, MD: I would say that tumor fraction is a really important prognostic factor. If you have lot of tumor DNA in the blood, you have probably a very large, extended, aggressive disease and then you have to escalate your treatment. If you have a low amount of no amount of DNA in the blood, then probably you have a less aggressive disease, you can think to deescalate. Narjust Florez, MD: Well, thank you so much for your time. This is very noble approach and we can wait to hear more about you in the future. Filippo Gustavo Dall'Olio, MD: Thank you very much to you. Narjust Florez, MD: Thanks.

Related Videos

Colorectal Cancer

Cathy Eng, MD, and Thejus Jayakrishnan, MD, on Colorectal Cancer: Metabolomic Differences in Young-Onset vs Average-Onset Disease

Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, and Thejus Jayakrishnan, MD, of the Cleveland Clinic Taussig Cancer Institute, discuss significant differences in the citrate cycle, a core pathway of cellular metabolism associated with colorectal cancer. Metabolomic differences impacted by environmental exposures (arginine biosynthesis and dietary red meat) were also noted, suggesting possible links with younger age of onset in this disease (Abstract 3510).

Leukemia

Claire Roddie, PhD, MBChB, on B-ALL: Safety and Efficacy Data of Obecabtagene Autoleucel

Claire Roddie, PhD, MBChB, of University College London, discusses results of the FELIX study, which showed that the second-generation chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel is safe for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, even those with a high burden of disease. This agent yielded high rates of complete response and ongoing CAR T-cell persistence in most patients whose disease responded (Abstract 7000).

Lymphoma

Catherine C. Coombs, MD, on B-Cell Malignancies and Long-Term Safety of Pirtobrutinib

Catherine C. Coombs, MD, of the University of California, Irvine, discusses prolonged pirtobrutinib therapy, which continues to demonstrate a safety profile amenable to long-term administration at the recommended dose without evidence of new or worsening toxicity signals. The safety and tolerability observed in patients on therapy for 12 months or more were similar to previously published safety analyses of all patients enrolled, regardless of follow-up (Abstract 7513).

Bladder Cancer

Christian Pfister, MD, PhD, on Bladder Cancer: New Overall Survival Data on Perioperative Chemotherapy

Christian Pfister, MD, PhD, of Rouen University Hospital, discusses phase III results from the VESPER trial, which showed that dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin provided a better overall survival rate at 5 years and improved disease-specific survival compared with gemcitabine as perioperative chemotherapy in patients with muscle-invasive bladder cancer (Abstract LBA4507). 

Skin Cancer
Immunotherapy

Jason J. Luke, MD, on Melanoma Adjuvant Therapy: Final Analysis of KEYNOTE-716

Jason J. Luke, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center, discusses adjuvant pembrolizumab, which, in previous results, improved distant metastasis– and recurrence-free survival in patients with resected stage IIB or IIC melanoma vs placebo. After a median follow-up of 39.4 months, adjuvant pembrolizumab continued to show a benefit over placebo, with no new safety signals (Abstract LBA9505).

Advertisement

Advertisement




Advertisement