As reported in The Lancet Oncology by Yu et al, based on results from the ongoing phase II NEOCAP trial, neoadjuvant therapy with the PD-1 inhibitor camrelizumab plus the angiogenesis inhibitor apatinib appears to demonstrate “promising” antitumor activity and a manageable toxicity profile in previously untreated patients with mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) locally advanced colorectal cancer.   

“Organ preservation seems promising not only in patients with rectal cancer but also in those with colon cancer who have a clinical complete response,” the investigators remarked. “[However,] close monitoring for immune-related adverse events and intensive patient management are needed to maximize patient benefit.”

Study Details

In the single-arm study, a total of 53 patients aged 18 to 75 years (median age = 54.5 years) with dMMR, MSI-H, or POLE/POLD1-mutated disease and an Eastern Cooperative Oncology Group performance score of 0 to 1 received 200 mg of intravenous camrelizumab on day 1 and 250 mg of oral apatinib on days 1 to 14 every 3 weeks. Those who achieved a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. Follow-up data were provided for a median of 16.4 months.

The primary endpoint of the trial was the proportion of patients with a pathologic or clinical complete response. The investigators also reported the objective response rate (defined as the proportion of patients with a clinical complete or partial response) and rates of treatment-related toxicities.

Clinical and Pathologic Complete Responses

More than half (54%) of the 52 activity-evaluable patients achieved a clinical complete response. Of these responders, 86% were managed with a watch-and-wait approach and showed no tumor regrowth at data cutoff. A total of 44% of patients underwent surgery for the primary tumor, of whom 61% achieved a pathologic complete response. Nearly three-quarters of the population—73%—achieved a complete response. The objective response rate was 92%.

Adverse Events

Any-grade adverse events were reported in 98% of patients. Hemangioma (47%), increased aminotransferase levels (47%), rash (45%), hypertension (36%), and stomatitis (26%) were the most commonly reported events.

A total of 38% of patients experienced a grade 3 to 5 adverse event, with elevated aminotransferase levels (11%), bowel obstruction (8%), and hypertension (8%) being the most frequently reported. Drug-related serious adverse events, including immune-related hepatitis, diabetic ketoacidosis, and bowel obstructions, were documented in 11% of the population. One patient died because of treatment-related immune-related hepatitis (grade 5 increased aminotransferase levels).

“These findings highlight the feasibility of neoadjuvant anti–PD-1–based therapy as an alternative to radical surgery,” the investigators concluded. “Our results indicate that the watch-and-wait approach could be an alternative treatment option for patients who seek organ preservation after having a clinical complete response following immunotherapy.” However, extended follow-up and large phase III trials are required to further validate the results and evaluate the benefit-to-toxicity ratio, the investigators noted.

Pei-Rong Ding, MD, of Sun Yat-sen University, Guangzhou, China, is the corresponding author of the article in The Lancet Oncology.

Disclosure: The study was funded by the National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For full disclosures of the study authors, visit thelancet.com.