Keytruda gets expanded coverage for 11 indications at cancer disease panel
After nearly two years of stalled discussions, the Keytruda (pembrolizumab) reimbursement expansion debate has finally begun.
The Cancer Disease Review Committee (CDRC) under the Health Insurance Review and Assessment Service (HIRA) set reimbursement standards for 11 of Keytruda's 17 indications.
On Wednesday, HIRA released the results of this year's first CDRC meeting's deliberations on the reimbursement for drugs used for cancer patients.
According to HIRA, the three new drugs on the agenda—Astellas' Padcev (enfortumab vedotin), Vyloy (zolbetuximab), and Pfizer's Elrexpio (elranatamab)—failed in their first reimbursement challenge.
Padcev is the first antibody-drug conjugate (ADC) developed to treat urothelial carcinoma. Astellas failed in its bid for coverage as a “combination therapy with pembrolizumab as first-line treatment for adult patients with locally advanced or metastatic urothelial carcinoma.
The Padcev combination therapy has been hailed as a turning point in urothelial cancer treatment, with the EV-302 study showing a 53 percent reduction in the risk of death compared to conventional platinum-based chemotherapy.
The U.S. National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines now recommend the combination as the first-line treatment of choice for patients with previously untreated metastatic urothelial cancer. The ESMO guidelines recommend that conventional chemotherapy be used only when the combination is contraindicated or unavailable.
Vyloy is a first-in-class targeted therapy to treat Claudin 18.2 (CLDN18.2)-positive gastric cancer. Astellas has filed for reimbursing Vyloy combined with fluoropyrimidine and platinum-based chemotherapy as first-line treatment for patients with CLDN18.2-positive, HER2-negative, unresectable, locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
In a global phase 3 clinical program (the SPOTLIGHT and GLOW studies), Vyloy significantly improved progression-free survival (PFS) and overall survival (OS) combined with conventional chemotherapy and was included in the NCCN guidelines as a priority recommendation (Category 1). It was also listed as a high-level recommendation in the Korean Gastric Cancer Practice Guideline Revision (5th Edition) released in January. However, it failed to pass the CDRC threshold for reimbursement, the first gate toward coverage.
Elrexpio is a bispecific antibody treatment that targets BCMA and CD3. Pfizer has applied for reimbursement as “monotherapy for treating adult patients with relapsed or refractory multiple myeloma who have received three or more prior therapies, including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies.”
Approved based on early clinical trial data, Elrexpio, like other bispecific antibody therapies that have failed to gain approval, was largely due to a lack of long-term follow-up data.
Despite the negative news, the CDRC meeting drew attention, as it was expected to discuss the stalled Keytruda reimbursement expansion issue.
In June 2023, MSD Korea submitted a batch of benefit expansion applications for 13 cancers with high unmet medical need. The company applied for four more indications, bringing the total to 17 additional Keytruda indications for review.
Of these, 11 indications passed the CDRC.
They include:
▲PD-L1 expression positive (CPS≥1), trastuzumab in combination with fluoropyrimidine and platinum chemotherapy for the first-line treatment of patients with inoperable locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
▲ Trastuzumab in combination with fluoropyrimidine and platinum-based chemotherapy for the first-line treatment of patients with inoperable locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma
▲ PD-L1 expression positive (CPS≥10) in combination with fluoropyrimidine and platinum-based chemotherapy for the first-line treatment of patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, combination therapy with platinum and fluoropyrimidine-based chemotherapy as first-line treatment in patients with inoperable locally advanced or metastatic esophageal cancer
▲ Confirmed progression after prior systemic therapy and ineligible for surgical or radiation therapy, combination therapy with lenvatinib for the treatment of advanced endometrial cancer without high-frequency microsomal instability (MSI-H) or defective mismatch repair (dMMR)
▲ MSI-H or dMMR, which are inoperable or metastatic
▲ Monotherapy and combination with platinum and fluorouracil (5-FU) chemotherapy in patients with PD-L1 expression positive (CPS≥1) as first-line treatment in patients with metastatic or inoperable recurrent squamous cell carcinoma of the head and neck
▲ PD-L1 expression positive (CPS≥1) and persistent, combination therapy with chemotherapy with or without bevacizumab for the treatment of patients with recurrent or metastatic cervical cancer
▲ Combination therapy with chemotherapy for the treatment of patients with PD-L1 expression-positive (CPS≥10), locally recurrent or metastatic triple-negative breast cancer that is inoperable and has progressed after prior therapy and for which there are no satisfactory alternative treatment options, treatment of patients with inoperable or metastatic endometrial cancer with MSI-H or dMMR
▲ Treatment of patients with inoperable or metastatic small bowel cancer with MSI-H or dMMR that has progressed after prior treatment and for which there are no satisfactory alternative treatment options
▲ Treatment of patients with inoperable or metastatic biliary tract cancer with MSI-H or dMMR that has progressed after prior treatment and for which there are no satisfactory alternative treatment options.
On the other hand, indications for relatively advanced stages, such as postoperative adjuvant therapy in non-muscle invasive bladder or renal cell carcinoma and perioperative adjuvant therapy in triple-negative breast cancer, failed to pass the threshold.
The remaining six indications that did not pass the review include:
▲ Treatment of BCG-refractory high-risk non-muscle-invasive bladder cancer with intraepithelial carcinoma with or without papilloma, for which cystectomy is not feasible or is not an option
▲ Monotherapy as postoperative adjuvant therapy for patients with renal cell carcinoma who are at intermediate- or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions
▲ Monotherapy for patients who have progressed after prior therapy and have no satisfactory alternative treatment options, MSI-H or dMMR, and inoperable or metastatic gastric, ovarian, or pancreatic cancer
▲ Combination with chemotherapy as preoperative adjuvant therapy, followed by monotherapy as postoperative adjuvant therapy in patients with high-risk early triple-negative breast cancer.
Besides, Novartis' chronic myeloid leukemia treatment, Scemblix (asciminib), and an injection of the immunosuppressant methotrexate were approved for coverage.