Padmanee Sharma, MD, PhD, professor of Immunology in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses immune checkpoint resistance in genitourinary (GU) cancers.

Sharma says that one of the ways to combat immune checkpoint resistance in patients with GU cancers is to use a combination approach. There are many trials addressing that in bladder cancer, such as an anti-CTLA4 agent plus an anti—PD-1/PD-L1 agent, which has shown promise in other tumor types.

In April 2018, the FDA approved the combination of the PD-1 inhibitor nivolumab (Opdivo) with the CTLA4 inhibitor ipilimumab (Yervoy) as a frontline treatment for intermediate- and poor-risk patients with advanced renal cell carcinoma (RCC). Sharma says that with this success, it is important to consider moving combination immunotherapy into earlier settings. Antiangiogenesis inhibitors and tyrosine kinase inhibitors are a big part of RCC, Sharma says, and may prove beneficial in combination with immunotherapy.

Sharma concludes that prostate cancer is the next realm of GU cancers to focus on regarding immunotherapy.

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Padmanee Sharma, MD, PhD, professor of Immunology in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses immune checkpoint resistance in genitourinary cancers.
 

Dr. Sharma Discusses Immune Checkpoint Resistance in GU Cancers

Padmanee Sharma, MD, PhD, professor of Immunology in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses immunotherapy in prostate cancer.

Immunotherapy has yet to find a foothold in the treatment of prostate cancer. Sharma says that in a recently-published paper in Nature, anti—CTLA-4 was given in a pre-surgical trial. Patients who were scheduled for surgery were given an anti–CTLA-4 agent and then their tumors were evaluated. Sharma says that this is one of her preferred ways of evaluating new agents, because there is access to all the tumor samples.

At baseline, there is not a lot of PD-1/PD-L1 expression in prostate cancer, Sharma explains. After anti—CTLA-4 was given, an increase in PD-1/PD-L1 expression was observed, suggesting that it can evolve over time. Sharma says that this should have been expected, as immune response is something that evolves over time—it is not static. Based on these data, Bristol-Myers Squibb has agreed to a trial testing the combination of an anti–CTLA-4 and anti–PD-1 agent. Sharma says from her own experience, patients with prostate cancer have done extremely well with this combination.  

Padmanee Sharma, MD, PhD, professor of Immunology in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses immunotherapy in prostate cancer.
 

Dr. Sharma Discusses Immunotherapy in Prostate Cancer

Padmanee Sharma, MD, PhD, scientific director, Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, discusses updated findings from the CheckMate-275 trial in bladder cancer during an interview at the 2018 AACR Annual Meeting.

Results from the CheckMate-275 trial previously confirmed the efficacy and safety of nivolumab (Opdivo) monotherapy in this population. Updated data showed that, at a median follow-up of 24.5 months, the overall response rate was 20.4% for all treated patients. In addition to the previously reported 17 complete responses (CRs), this update showed 9 more CRs.

Sharma says that immunotherapy should be considered as one of the primary pillars in treating patients with metastatic bladder cancer. She adds that there is a lot of information available on how to administer and manage patients on immunotherapies for the community oncologist.

Dr. Sharma Discusses Updates from CheckMate-275 in Bladder Cancer

Padmanee Sharma, MD, PhD, professor of Immunology, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses PD-L1 as a predictive biomarker for immunotherapy in patients with bladder cancer.

PD-L1 as a biomarker is generating much excitement in the field of bladder cancer, as anti—PD-1/PD-L1 agents have demonstrated promise in these patients, Sharma explains.

However, Sharma cautions that PD-L1 may not be the most accurate and predictive biomarker, as it changes over time and does not present a clear picture of the evolving immune response. Other biomarkers, including CD8 T cells, CD45RA cells, and Granzyme B may be worth investigating, she adds.

Padmanee Sharma, MD, PhD, professor of Immunology, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses PD-L1 as a predictive biomarker for immunotherapy in patients with bladder cancer.


Padmanee Sharma, MD, PhD

Articles

Dr. Sharma Discusses Immune Checkpoint Resistance in GU Cancers

Dr. Sharma Discusses Immunotherapy in Prostate Cancer

Dr. Sharma Discusses Updates from CheckMate-275 in Bladder Cancer

Dr. Sharma on PD-L1 as Biomarker for Immunotherapy in Bladder Cancer