Preoperative Immunotherapy in Oncology

Immune checkpoint inhibitors (ICI) are in standard use for the treatment of many kinds of metastatic tumor. Their use before surgery to prolong event-free and overall survival (EFS, OS) has been studied in recent years.

This review is based on clinically relevant studies published since 2018 on the preoperative use of ICI for four tumor entities: breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, and esophagogastric adenocarcinoma. The studies were identified by a selective search in PubMed. In addition, abstracts from international conference presentations were evaluated.

The approved, standard perioperative treatment of triple-negative breast cancer of stage IIa and above is with durvalumab (an ICI) combined with chemotherapy for one year. This improved the 5-year EFS by 9% (81.2% vs. 72.2%; HR = 0.65) and the overall survival rate by 5% (86.6% vs. 81.7%; HR = 0.66). In NSCLC, the addition of an ICI to preoperative chemotherapy increased 2-year EFS by approximately 11% in stage II or III (63.3% vs. 52.4%; HR = 0.68), according to the largest trial that has been published to date. The addition of durvalumab to perioperative chemotherapy for stage II or III esophagogastric adenocarcinoma increased the 2-year EFS by 8% (67% vs. 59%; HR = 0.71). Approval for this indication is expected. In colorectal carcinoma with microsatellite instability, neoadjuvant ICI therapy for 1-6 months often led to clinical and/or histological complete remission. In view of the high remission rates (50%-100%), patients with rectal carcinoma may be spared surgery and the particular risks it entails.

For some types of tumor, neoadjuvant ICI therapy is standard and/or about to be approved. Special care must be taken in managing ICI toxicity. In view of the adverse effects and cost of ICI, it will be important to identify biomarkers for a higher likelihood of benefit.