Landscape of subsequent therapies in perioperative immunotherapy trials across multiple cancer types

Abstract

Section snippets

Patients receiving subsequent therapy

Initially, we assessed the number of patients in the control groups who underwent any subsequent treatment (including surgery, radiotherapy, or systemic therapy) after a disease-free survival event. Among the 15 perioperative ICI trials examined, only eight trials provided data on the number of patients receiving any subsequent therapy. In the melanoma clinical trials, 62 (89·8%) of 69 patients (CheckMate 76K) and 282 (87·3%) of 323 patients (EORTC 18071) who had a disease-free survival event

Patients receiving subsequent systemic therapy

We examined the number of patients who underwent systemic therapy following disease-free survival events in the control group. Among the 15 perioperative ICI trials examined, 13 provided data on the number of patients receiving subsequent systemic therapy. In the melanoma trials, 44 (38·2%) of 115 patients (KEYNOTE-716), 49 (71·0%) of 69 (CheckMate 76K), and 218 (72·2%) of 302 (KEYNOTE-054) who experienced a disease-free survival event received systemic therapy. In the NSCLC trials, 131 (61·8%)

Patients receiving subsequent immunotherapy

We then reviewed the proportion of patients receiving subsequent systemic immunotherapy among the patients who experienced a disease-free survival event in the control or non-experimental group. In the melanoma trials KEYNOTE-716 and KEYNOTE-054, which were the only trials with a built-in cross-over, 35 (30·4%) of 115 patients (KEYNOTE-716) and 195 (64·6%) of 302 (KEYNOTE-054) with a disease-free survival event received ICI as subsequent therapy. In the NSCLC trials, 102 (48·1%) of 212 patients

Non-immune subsequent systemic therapy

Relapses after surgery in some types of cancers are typically aggressive and surveillance or local therapies are not recommended. An example is urothelial carcinoma, for which regular radiology monitoring within adjuvant trials should enable early detection, necessitating timely intervention.⁵ Chemotherapy has been considered the global standard of care for the management of patients with metastatic urothelial carcinoma and is globally available. Therefore, upon relapse, most patients should

Real-world scenarios after recurrence

To further understand the vast range of scenarios following tumour relapses, we created a visualisation of real-world instances of reporting subsequent therapies in perioperative trials, specifically focusing on renal cell carcinoma from KEYNOTE-564 (appendix p 3), the only pure adjuvant immunotherapy trial in solid cancers with an overall survival benefit. Our point was to illustrate that analyses of subsequent therapies are time-dependent and complex. For instance, by capturing subsequent

Discussion

Only a subset of patients seem to receive subsequent therapies in perioperative trials, suggesting some unmet needs in practice, from education and health-system organisation to accessibility to standard and innovative treatments. Potential gaps in clinical trials data collection are also possible and could be attributed to challenges in keeping track of patients in long-term clinical trials, or even entering data appropriately.11, 12 A review by Fitzpatrick and colleagues¹³ showed that longer