FOIU 2018: Immunotherapy as an Early Treatment? What Have We Learned From Other Malignancies?

Tel Aviv, Israel (UroToday.com) Daniel Goldstein, MD, gave a talk on the possibility of immunotherapy given as at an earlier stage. The role of immunotherapy in the adjuvant/neoadjuvant setting is still being explored and studied. The utility of immunotherapy in metastatic urologic cancers is still being analyzed. There are distinct phases of treatment effect in immunotherapy, as can be seen in Figure 1.



Figure 1 – Treatment phases:
Figure1_treatment_phases.png

Dr. Goldstein continued to discuss how much durable response exists in immunotherapy in genitourinary cancers. The most accurate answer to this question is that we really do not know. However, it is possible to use statistical models to estimate a response to this question, as can be shown in Figure 2, using Pembrolizumab for first line PD-L1 positive non-small cell lung cancer.

Figure 2 – Using statistical models to estimate durable survival:
Figure2_Durable_Survival.png

The next question asked by Dr. Goldstein is whether the durable survival is unique to immunotherapy in bladder cancer. As the graphs in Figure 3 demonstrate, this also occurs in chemotherapy treatment. Next, Dr. Goldstein asked if chemotherapy is sometimes better than immunotherapy (Figure 4).

Figure 3 – Durable survival in Chemotherapy:
Figure3 Durable Survival Chemotherapy

In May 2014, The FDA issues a warning against single agent checkpoint inhibition for PD-L1- low untreated urothelial carcinoma. One possible reason for this warning is that the response rate with gemcitabine/cisplatin chemotherapy is 49%1, while with immunotherapy the response rate is 21%2.

Figure 4 – Chemotherapy better than immunotherapy?
Figure4 Chemo Immunotherapy

Lastly, Dr. Goldstein presented a pharmacoeconomic analysis of personalized dosing vs. fixed dosing of pembrolizumab in first-line PD-L1 positive non-small cell lung cancer, demonstrating that personalized dosing can save 0.8 billion US dollars per year!3

Dr. Goldstein concluded his talk by stating that the role of biomarkers in immunotherapy is going to be critical in the future, and will help predict response for this type of therapy. He reiterated the importance of personalized dosing and its beneficial financial aspect and said that the role of immunotherapy, whether in the adjuvant or neoadjuvant setting, requires further exploring.

Presented by: Daniel Goldstein, Rabin Medical Center, Petach-Tiqva, Israel and University of North Carolina, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel

References:
1. von der Maase, JCO 2000
2. Bellmunt et al. NEJM 2017
3. Goldstein D. et al. JNCI 2017