Treatment Combinations Based in Immune Checkpoint Inhibitors Provide Survival Benefits in CRC

Treatment combinations based on immune checkpoint inhibitors (ICI) provided survival benefits for patients with heavily pretreated microsatellite stable (MSS) metastatic colorectal cancer (mCRC), according to a study published in the American Journal of Cancer Research.¹ The treatment was found to have a good safety profile in patients who received it.

Heavy disease burden and high incidence of CRC are found in China,² which is in line with the global incidence of CRC. Incidence and mortality related to CRC have increased in China in the past 20 years, with 25% of patients diagnosed with mCRC at diagnosis, which only has a 12% survival rate. ICIs have been used to improve both survival and prognosis in cancer, especially certain types of mCRC. This study aimed to assess the efficacy and safety of regimens based on ICIs for use as a third-line treatment in MSS mCRC.

This study was conducted at the Renmin Hospital of Wuhan University in China and included patients treated at the cancer center between June 2019 and April 2024. Patients were included if they were aged 18 years or older, had received at least a second-line treatment, had metastatic and/or progressive mismatch repair-proficient/MSS colorectal adenocarcinoma, had at least 1 measurable lesion, had adequate organ function, and had a life expectancy of 3 months or more. Incomplete medical data, reception of immunosuppressive therapy, or a history of active autoimmune disease or organ transplantation were reasons for exclusion.

Patients with metastatic colorectal cancer had survival benefits when taking ICIs combined with TKIs with or without chemotherapy | Image credit: Dr_Microbe - stock.adobe.com

Medical records and lab results were used for this study, with the primary end point being progression-free survival (PFS) and overall survival (OS). Objective response rate (ORR), safety and prognostic analyses, and disease control rate (DCR) were the secondary end points of the study. Efficacy and safety analyses included any patient who had at least 1 dose of the ICI. All adverse events, including those related to treatment and the immune system, were collected from all patients.

There were 143 patients with MSS mCRC who were included in the study. The median (IQR) age of the patients was 59 (51-67) years and 68.5% were men. Most of the cohort had 2 metastatic organs (75.5%), with 65.0% having liver metastasis, and 76.9% of the tumors were located in the left-side colon and rectum. Surgical resection occurred in 83.2% of the patients.

A total of 55.2% of the patients chose to use ICI with a tyrosine kinase inhibitor (TKI), whereas 18.9% received ICI combined with TKI and chemotherapy, 14.0% received ICI with large molecular targeted drugs, 13.3% received ICI and chemotherapy, and 4.9% received only ICI. Only 56 of the patients survived through April 2024. The intention to treat population had an ORR of 11.2% (95% CI, 6.7-17.8) and a DCR of 72.7% (95% CI, 64.5-79.7). The third-line cohort had an ORR of 12.5% (95% CI, 6.7-21.7) and a DCR of 79.6% (95% CI, 69.4-87.1)

The median OS was 11.8 months (95% CI, 10.2-13.4), and the median PFS was 4.6 months (95% CI, 4.1-5.1). There were no significant differences found between the OS and PFS of the third-line cohort compared with the fourth-line or higher. The patients who had cross-line therapy had a significant improvement in OS compared with those who did not (15.8 months vs 10.2 months). Worse median PFS was found in patients with liver metastasis compared with those who didn’t (3.5 months vs 6.7 months). Liver metastasis also acted as a prognosis factor for OS (HR, 1.77; 95% CI, 1.06-2.96) and PFS (HR, 2.35; 95% CI, 1.54-3.59).

The shortest median PFS was found in those who received ICI alone, who had a PFS of 2.5 months (95% CI, 0.0-4.9). In contrast, a median PFS of 4.4 months was found in those who took combinations of ICI plus TKI and ICI plus large molecular targeted drugs plus chemotherapy. The median OS was 14.3 months (95% CI, 4.6-24.1) in patients who had ICI plus TKI and chemotherapy compared with those who had ICI plus chemotherapy. At least 1 treatment-related adverse event was found in 93.9% of the patients, but most were grades 1 and 2. A total of 42.0% had an incidence of immune-related adverse events.

There were some limitations to this study. Selection bias is possible due to the study design. The statistical power is reduced due to the small sample size. Comorbidities could influence the findings. The PD-L1 combined positive score and tumor mutation burden were unknown in most patients.

The researchers concluded that ICI plus TKI, either with or without chemotherapy, was able to demonstrate meaningful survival improvement. “This real-world clinical outcome may provide reliable data support for further clinical studies of immunotherapy rechallenge in patients with MSS CRC,” the authors wrote.

References

1. Zhao W, Chen Y. Efficacy and safety of immune checkpoint inhibitors in heavily pretreated patients with microsatellite stable metastatic colorectal cancer: a real-world retrospective study. Am J Cancer Res. 2024;14(11):5378-5388. doi:10.62347/KAFY8529
2. Zhou J, Zheng R, Zhang S, et al. Colorectal cancer burden and trends: comparison between China and major burden countries in the world. Chin J Cancer Res. 2021;33(1):1-10. doi:10.21147/j.issn.1000-9604.2021.01.01