Immunotherapy in GU Cancers

Pedro C. Barata, MD, MSc, discusses the importance of further exploring the facets of manipulating the microbiome to augment responses with immunotherapy in RCC, as well as the promise of the bifidogenic live bacterial product, CBM588.

Kidney and renal pelvis cancers are one of the 10 most common new malignant diagnoses in both men and women in the United States, with an estimated 52,360 new cases in men and 29,440 new cases in women per year.

Rohit Kumar, MD, discusses the benefits of TKI/immunotherapy doublets in renal cell carcinoma, unmet needs regarding future research with triplet therapies in the frontline setting, and how hypoxia inducible factor inhibitors may play a role in the treatment of patients who have progressed on prior TKI/immunotherapy combinations.

CYNK-101 demonstrated synergistic activity when used in combination with avelumab through antibody-dependent cellular cytotoxicity against PD-L1–positive non–small cell lung cancer, triple-negative breast cancer, and bladder cancer cell lines, according to preclinical data.

The European Commission has approved the combination of pembrolizumab and lenvatinib for the treatment of patients with advanced renal cell carcinoma.

The combination of CG0070 and pembrolizumab was well tolerated and demonstrated early signals of activity in patients with Bacille Calmette-Guérin-unresponsive non–muscle invasive bladder cancer.

Nivolumab plus cabozantinib continued to significantly improve overall response rate vs sunitinib in patients with previously untreated, advanced renal cell carcinoma, with meaningful response outcomes observed irrespective of dose modifications with cabozantinib and fewer responders in the doublet arm requiring subsequent treatment.

The FDA has granted a full approval to pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing chemotherapy.

The investigational RNA interference therapy, ARO-HIF2, was shown to have encouraging signals of activity with favorable tolerability in heavily pretreated patients with advanced clear cell renal cell carcinoma.

Adjuvant nivolumab led to a significant improvement in disease-free survival compared with placebo in patients with high-risk muscle-invasive urothelial carcinoma following radical surgery, irrespective of PD-L1 expression level.

In a 10 to 1 vote, the FDA’s Oncologic Drugs Advisory Committee voted to support the accelerated approval of atezolizumab for the frontline treatment of patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma.

The FDA’s Oncologic Drugs Advisory Committee is poised to move forward this week with a public review of 6 indications for immune checkpoint inhibitors granted under the agency’s accelerated approval process that later failed to reach thresholds for statistical significance for key end points in confirmatory clinical trials.

The European Commission has approved the combination of nivolumab and cabozantinib as a frontline treatment in patients with advanced renal cell carcinoma.

Data from the phase 3 CheckMate-9ER trial has not only confirmed the advantage of cabozantinib plus nivolumab in terms of progression-free survival, overall survival, and responses vs sunitinib in the frontline treatment of patients with advanced renal cell carcinoma, but it has served as additional incentive to push the needle even further with research aimed at evaluating triplet regimens in the frontline setting and response-guided sequencing strategies.

Immunotherapy is now incorporated into National Comprehensive Cancer Network guidelines as maintenance therapy and in a sequencing strategy for the treatment of patients with metastatic urothelial carcinoma and in the setting of superficial UC-carcinoma in situ with prior intravesical therapy.

Six indications for immune checkpoint inhibitors granted under the FDA’s accelerated approval process that later failed confirmatory clinical trials are being reassessed as the agency continues an industry-wide evaluation of the pathway.

The combination of nivolumab and cabozantinib showcased significant benefit in terms of progression-free survival, overall survival, and responses vs sunitinib in the frontline treatment of patients with advanced renal cell carcinoma, as was underscored in data from the phase 3 CheckMate-9ER trial.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for the combination of cabozantinib plus nivolumab for use as a frontline treatment in patients with advanced renal cell carcinoma.

Claud N. Grigg, MD, highlights different frontline combination regimens that are improving outcomes for patients with metastatic renal cell carcinoma.

February 12, 2021 - Atezolizumab monotherapy showed favorable outcomes compared with chemotherapy alone as frontline treatment for patients with cisplatin-ineligible IC2/3 advanced or metastatic urothelial carcinoma.

February 11, 2021 - First-line treatment with immune checkpoint inhibitor–based regimens could be linked with an improvement in overall survival versus select targeted therapies in patients with metastatic non–clear cell renal cell carcinoma.

The emergence of checkpoint inhibitors has transformed the second-line treatment of patients with metastatic bladder cancer. However, questions regarding the utility of immunotherapy in the frontline setting remain unanswered, leaving chemotherapy as the standard-of-care option.

Circulating tumor DNA positivity identified patients with high-risk muscle-invasive urothelial cancer who were likely to derive improvements in disease-free survival and overall survival from adjuvant atezolizumab vs observation.

Combination regimens comprised of immunotherapy and TKI inhibitors have yielded significant benefits in terms of overall survival and progression-free survival with acceptable safety in patients with renal cell carcinoma; however, the cost of these regimens may negate the impact of these advances.

The combination of lenvatinib plus pembrolizumab demonstrated encouraging antitumor activity in patients with metastatic clear cell renal cell carcinoma who had progressed on prior PD-1 or PD-L1 immune checkpoint inhibitor therapy.

The combination of preoperative nivolumab and ipilimumab demonstrated preliminary feasibility and safety in patients with locoregionally advanced urothelial cancer.

Scott Tykodi, MD, PhD, discusses the FRACTION-RCC study and other novel combinations under exploration for heavily pretreated patients with advanced renal cell carcinoma.

The investigational PD-L1 inhibitor BGB-A333 in combination with the PD-1 inhibitor tislelizumab demonstrated marked antitumor activity, durable clinical responses, and a tolerable safety profile in patients with urothelial carcinoma.

Bradley McGregor, MD, discusses some of the recent approaches that have emerged in bladder cancer and renal cell carcinoma, as well as anticipated developments in each field.

Guru P. Sonpavde, MD, discusses several trials in the field of first-line metastatic urothelial cancer that are testing combinations with gemcitabine/platinum-based therapy followed by maintenance avelumab.