Keytruda Improves Progression-Free Survival for Advanced Colorectal Cancer Patients


Findings of the interim analysis from KEYNOTE-177 were presented at the virtual scientific meeting of the American Society of Clinical Oncology (ASCO) held in May 2020.

The lead author of the Phase III trial was Dr. Thierry André of the Université Sorbonne, Paris. Dr. Thierry commented that the study shows the huge benefit of pembrolizumab (Keytruda) and that this immune checkpoint inhibitor should become the new standard of care.

This opinion was also expressed by ASCO President Dr. Howard Burris III. Dr. Burris explained that immunotherapies have now entered the realm of first-line treatments for advanced cancers with a substantial number of mutations. One such example is metastatic colorectal carcinoma.

Genetic Signatures

This type of advanced cancer has specific genetic signatures such microsatellite instability and/or mismatched repair deficiency (MMR).

Microsatellite instability describes cells having changes in genes that correct mistakes when DNA is being copied in a cell.

MMR deficient cells carry a significant number of DNA mutations. These mutations generally lead to cancer or at a minimum they indicate a poor prognosis. DNA mutations are mostly found in colorectal cancer.

According to previous research, these tumors indicate a risk of poor survival and patients respond poorly to conventional chemotherapy.

Pembrolizumab functions by blocking a receptor called PD-1 which is a protein that assists in controlling the immune system. Pembrolizumab releases the brakes on PD-1 and allows the immune system to go on the attack against cancer cells.

Phase III KEYNOTE-177 Clinical Trial (NCT02563002)

The trial involved three hundred seven patients who had cancer that spread to other parts of the body (metastatic disease). Progression-free survival and overall survival were the primary endpoints.

The secondary endpoints were safety and overall response rate.

The key findings at the twelve-month mark were progression-free survival (PFS) of fifty-five percent for patients given pembrolizumab. This compares quite favorably at the same interval against thirty-seven percent for patients receiving chemotherapy.

At a twenty-four month follow up, the PFS for patients receiving pembrolizumab was forty-eight percent versus eighteen percent for patients receiving chemotherapy.

About Toxicity

Toxicity differed widely between the two therapies. Some patients in the pembrolizumab group experienced immune-mediated events such as hepatitis or colitis.

The common adverse events from chemotherapy toxicities were neutropenia (infection-fighting white blood cells), nausea, fatigue, hair loss, and neurotoxicity (toxins affecting the nervous system).

Treatment-related events were also not as frequent among patients treated with pembrolizumab (22%) versus chemotherapy (66%).

Patients in the chemotherapy group were able to join the pembrolizumab group upon disease progression.

The investigators will continue to monitor patients for overall survival.

About ASCO

The American Society of Clinical Oncology (ASCO) represents over forty-five thousand people in the oncology profession. Research and education for ASCO are funded by the ASCO Foundation.

What are your thoughts about the potential of pembrolizumab versus chemotherapy? Share your stories, thoughts, and hopes with the Patient Worthy community!

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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