Using non-randomized trials to assess the clinical benefit of systemic anti-cancer treatments: Viable or not?

Background: The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs).

Interval Metastases After Neoadjuvant Chemoradiotherapy for Patients with Locally Advanced Esophageal Cancer: A Multicenter Observational Cohort Study.

Background: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival.

Assessing the clinical benefit of systemic anti-cancer treatments in the Netherlands: The impact of different thresholds for effectiveness.

Background: In the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs.

Cost-effectiveness and budget impact of pembrolizumab+axitinib versus sunitinib in patients with advanced clear-cell renal cell carcinoma in the Netherlands.

Background: The phase 3 clinical trial KEYNOTE-426 suggested a higher efficacy regarding overall survival (OS) and progression-free survival (PFS) of pembrolizumab+axitinib compared to sunitinib as a first-line treatment for patients with advanced renal cell carcinoma. In this analysis, the potential cost-effectiveness of this combination treatment versus sunitinib for patients with advanced clear-cell renal cell carcinoma (accRCC) was examined from the societal perspective in the Netherlands.

Methods: For this analysis, a partitioned survival model was constructed.

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

Background: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma.

Methods: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight).