ASCO Honolulu: Dr Acoba Discusses the Use of Immunotherapy in Colorectal Cancer

Presented by:

Jared Acoba, MD, Associate Researcher, University of Hawaii Cancer Center

Meeting:

ASCO Direct Honolulu, 2024

 The Bottom Line:

Based on previous findings, immunotherapy before surgery (neoadjuvant treatment) has been established as the standard of care for a specific subset of rectal cancer patients with locally advanced disease, and recently reported long-term results further reinforce these guidelines.  A new study suggests that a similar subset of colon cancer patients may also benefit from neoadjuvant immunotherapy, but further research is needed to establish this approach as standard of care in patients who are otherwise amenable to curative intent surgery.

Background:

Immunotherapy is a type of anticancer treatment that enables the body’s immune system to more effectively recognize and target cancer cells for destruction.  In a previous study, the use of neoadjuvant (pre-surgery) immunotherapy with dostarlimab led to complete responses for a subset of patients with a specific type of rectal cancer that is termed mismatch repair deficient (dMMR), and this therapy has now become standard of care for such patients.  Two abstracts from this year’s meeting of the American Society for Clinical Oncology (ASCO), highlighted by Dr Acoba, examined the use of neoadjuvant immunotherapy in colorectal cancer (CRC); one reported an update to the aforementioned trial, and another examined a similar approach, applied to colon cancer patients.  

Trial Design and Patients:

The first abstract was a follow up to the ‘MSK study’ in dMMR rectal cancer patients with stage II or III locally advanced disease.  Patients received neoadjuvant dostarlimab and those who achieved a clinical complete response (cCR), with no evidence of residual disease, went on to a ‘watch and wait’ approach, with no further treatment.  Dr Acoba noted that, to date, 100% of the 42 patients in the trial have achieved the primary endpoint of cCR, meaning that there is no evidence of disease, and the patients do not require subsequent surgery or additional anticancer treatment.  The secondary endpoint in the trial examined whether these responses were durable at 12 months after therapy.

A second abstract Dr Acoba highlighted examined the use of 2 different types of immunotherapies (IBI310 and sintilimab) in combination, for dMMR patients with stage IIB – III colon cancer who were eligible for a surgical resection.  Patients in the trial received the immunotherapy combination, or sintilimab alone, and then went on to surgery, with the primary endpoint of pathologic complete response (pCR).  Notably, about 75% of patients in the trial were high risk, and had lymph node positive disease.

Main Trial Results:

The results from the MSK study of rectal cancer patients, at a median follow up of 26.3 months, demonstrated that all of the neoadjuvant immunotherapy responses were durable, with all patients continuing to show cCR, and no patients requiring chemotherapy, radiotherapy, or surgery.  There were also no grade 3 or 4 toxicities resulting from the immunotherapy.  Based on these results, a confirmatory phase III study is underway (AZUR1), and neoadjuvant immunotherapy has become the standard of care for locally advanced dMMR rectal cancer patients.

In the second study of immunotherapy in dMMR colon cancer, the vast majority of patients in the trial achieved the endpoint of pCR, with a rate of 78.4% in the combination arm and 46.7% in the sintilimab alone arm, and the difference between groups was statistically significant (P=0.0015).  While the overall adverse event profile was as expected with these agents, Dr Acoba noted there was a fairly high rate of grade 3 or 4 events (26.9% for the combination, and 18.4% with sintilimab alone), considering this population of patients had cancers that were amenable to curative intent surgery.

 Conclusions and Faculty Insights:

In summary, Dr Acoba noted that, based on the long term results of the MSK study in dMMR rectal cancer patients, further follow up has confirmed the initial positive results in terms of cCR rates with neoadjuvant immunotherapy to be durable, and this further reinforces the current standard of care.  By comparison, he believes the use of neoadjuvant immunotherapy for patients with dMMR CRC who are resectable as “not ready for prime time”, as it led to a fairly high rate of grade 3 and 4 adverse events for a population of patients who might otherwise be curable with surgery alone. Accordingly, Dr Acoba noted that, at present, this option is only recommended for patients with advanced and/or unresectable disease, while those whose disease is resectable should continue to be treated with surgery.

Speaker Disclosure Information:

Dr Acoba reported the following disclosures for this presentation:

Research funding from GSK