NICE Rejects Merck's Keytruda for Advanced Urothelial Cancer in Final Guidance

Compiled by Lili

On March 18, the UK National Institute for Health and Care Excellence (NICE) issued its second final evaluation document, rejecting Merck Sharp & Dohme’s Keytruda for the treatment of advanced bladder cancer.

The assessment document indicates that MSD can collect further evidence of efficacy for Keytruda under this indication, which will then be reviewed by NICE as part of its final determination.

In fact, in March 2020, NICE began its decision not to issue a permanent recommendation for Keytruda for this patient population, based on the randomized, pivotal Phase III clinical study KEYNOTE-045. This study was conducted in 542 patients with metastatic or locally advanced, unresectable urothelial carcinoma who had experienced disease progression or recurrence after prior platinum-containing chemotherapy. In this study, the 542 patients were randomized to receive either the PD-1 antibody pembrolizumab (200 mg every three weeks) or investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), duration of response (DoR), and safety. PD-L1 expression was quantified using the Combined Positive Score (CPS) of tumor cells and infiltrating immune cells.

The final results of the KEYNOTE-045 study showed that in second-line treatment, Keytruda provided a benefit in overall survival (OS) but not in progression-free survival (PFS). In a statement released today, NICE stated that although evidence indicated Keytruda met its criteria for “life-extending treatments,” the cost-effectiveness of immunotherapy remained uncertain. This uncertainty arose because it was unclear which treatment switching adjustment or overall survival modeling approach was most appropriate, and the duration of pembrolizumab’s therapeutic effect remained undetermined.

Following this rejection, although NICE maintained its previous guidance recommending against the use of Keytruda as second-line treatment for patients with advanced bladder cancer, MSD appealed the decision.

At MSD, the clinical development program for Keytruda comprises more than 400 clinical studies covering over 30 tumor types, with at least half of these studies investigating combination therapies of Keytruda with other agents. In bladder cancer, the company is advancing the largest oncology immunotherapy clinical development program in this field, encompassing 27 clinical studies to evaluate the potential of Keytruda as monotherapy and in combination regimens for the treatment of bladder cancer.

It is reported that Keytruda is the first anti-PD-1 therapy approved for adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have progressed after first-line treatment. In October 2020, the U.S. Food and Drug Administration (FDA) approved Keytruda as a monotherapy for the second-line treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL). Just a few days ago, the European Commission (EC) approved the first pediatric indication for Keytruda, announcing that the PD-1 inhibitor Keytruda, as a monotherapy, is indicated for the treatment of adult and pediatric patients aged ≥3 years with relapsed or refractory classical Hodgkin lymphoma (r/r cHL) who have failed autologous stem cell transplantation (ASCT) or who have received at least two prior therapies in cases where ASCT is not suitable as a treatment option.

Merck & Co., Inc. reported full-year revenue of $48 billion last year, a 2% year-over-year increase, with pharmaceutical sales reaching $43 billion and animal health revenue amounting to $4.703 billion. As Merck’s blockbuster product, Keytruda generated $14.4 billion in sales in 2020, representing a 30% year-over-year growth and contributing 33% of the company’s pharmaceutical business revenue.

Notably, in 2018, NICE approved Keytruda for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) who had experienced disease progression following prior platinum-containing chemotherapy, making Keytruda the first and only immuno-oncology therapy for UC to be included in the UK National Health Service (NHS).

Furthermore, in its statement, NICE recommended Roche’s anti-PD-L1 drug Tecentriq (atezolizumab) for bladder cancer patients at this stage of the treatment pathway.

References:

1. NICE rejects Keytruda for advanced bladder cancer in final guidance

2. European Commission approves Expanded Indication for Merck’s KEYTRUDA? (pembrolizumab) in Adult and Pediatric Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL)

3. FDA Accepts Two sBLAs for Merck’s KEYTRUDA (pembrolizumab) for Locally Advanced or Metastatic Urothelial Cancer in Cisplatin-Ineligible First-Line and Second-Line Post-Platinum Failure Treatment Settings