SUO 2017: Rationale, Pitfalls and Actionable Results of Genomic Testing in Developing Neoadjuvant and Adjuvant Strategies

Washington, DC ( Dr. Pal began his presentation by asking 3 critical questions regarding genomic testing in the adjuvant/neoadjuvant setting: 1. Does the biomarker have established predictive value? 2. Is there sufficient genomic material in localized disease? 3. What is the ease of acquiring samples for genomic testing?

He then moved on to discuss the topic of PD-L1 immune checkpoint (ICP) inhibitor, stating that in the Checkmate 214 trial, comparing Nivolumab + Ipilimubab to Sunitinib in renal cell carcinoma (RCC) patients there was a clear advantage to this combination in patients with PD-L1>=1%. In another trial, the Immotion 150 , which compared  Sunitinib to Atezolizumab and to Atezolizumab and Bevacizumab together, again, a clear advantage was shown in this treatment combination in patients with PD-L1 positive patients. However, gene signatures were shown to probably be better as a biomarker, when compared to PD-L1 status.

Next, Dr. Pal discussed the 16 gene recurrence score as a possible biomarker. This was evaluated in the S-TRAC trial, comparing adjuvant Sunitinb to placebo in the setting of RCC. Unfortunately the interaction of the recurrence score with treatment did not reach significance. The authors concluded that is could serve as a prognostic marker but not as a predictive marker.

Dr. Pal then discussed the role of blood and circulating tumor DNA (ctDNA) and showed that it may predict immunotherapy disease control rate. Dr. Pal summarized that the predictive value of ctDNA needs to be more firmly established and novel techniques may increase yield of ctDNA in localized patients.

Lastly Dr. Pal discussed stool microbiome profiling. From studies sequencing stool at various time points in patients treated with Sunitinib, it has been shown that data regarding its role as a predictive biomarker is still preliminary, but it is quite abundant so there is lots of genomic material available. It can be easily collected but storage/processing standardization is important.

Dr. Pal concluded his lecture by stating that there is a need to engage our translational colleagues as we design adjuvant/neoadjuvant trials to maximize yield.

Presented by: Sumanta Kumar Pal, MD. Associate Clinical Professor, Department of Medical Oncology & Therapeutics Research, Co-director, Kidney Cancer Program, Medical Oncologist, City of Hope, Duarte, CA 

Written by: Hanan Goldberg, MD @GoldbergHanan Society of Urologic Oncology Fellow University of Toronto, Princess Margaret Cancer Centre at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC