July 2015, Special ASCO Edition

← Back to Issue

Pembrolizumab in Colorectal Cancer: Can Benefit Be Predicted?

Immunotherapy

New to the programmed death-1 (PD-1) inhibitor arena is colo­rectal cancer, and for this tumor it may be possible to predict which patients will benefit from these drugs.

In a phase 2 study of patients with colorectal cancer treated with pembrolizumab, the presence of mismatch repair (MMR) deficiency within the tumor was associated with the greatest benefit. Almost two-thirds of patients with MMR deficiency responded to pembrolizumab (10 mg/kg every 2 weeks), but response was not observed among patients with MMR-proficient tumors, according to Dung T. Le, MD, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.

MMR deficiency occurs in up to 20% of sporadic colorectal cancers and in nearly all colorectal cancers associated with Lynch syndrome. Several other tumor types demonstrate MMR, a mechanism of DNA repair, and about 5% of these tumors may be MMR-deficient.

“This is the first study to use genetics to guide immunotherapy,” Le said.

She pointed out that tumors that are deficient in MMR proteins harbor “hundreds to thousands” of mutations. Since a high mutational load in a tumor increases the probability of recognition by the immune system, these tumors could be easy targets for PD-1 inhibitors.

In the study, MMR-deficient tumors expressed an average of 1782 mutations each, compared with 73 in MMR-proficient tumors. Higher numbers of mutations were linked to better responses to pembrolizumab.

The study included 3 groups of patients: metastatic colorectal cancer patients with MMR-proficient tumors (n = 25), a similar group with MMR-deficient tumors (n = 25), and patients with other types of metastatic tumors that were MMR deficient (n = 21).

When treated with pembrolizumab, 62% of the MMR-deficient cohort responded, compared with 0% of patients with MMR-proficient tumors; 60% of patients with noncolorectal MMR-deficient tumors also responded. Tumor regression or stabilization ?20 weeks was observed in 92%, 16%, and 70%, respectively, and many responses were ongoing for more than 1 year, Le reported.

Median progression-free survival was significantly increased in the MMR-deficient cohort but was not yet reached; it was only 2.3 months in the MMR-proficient cohort (P <.0001).

Le emphasized that MMR status is easily determined with a commercially available test and is already commonly used in patients with colorectal cancer.

The discussant of the trial, Neil Howard Segal, MD, PhD, Memorial Sloan Kettering Cancer Center, New York City, reiterated there was “clear benefit” for pembrolizumab in patients with MMR deficiency; however, this is a small subgroup among all patients with colorectal cancer. Nevertheless, for this group, he suggested, “there is potential for change in clinical practice” in the treatment of metastatic colorectal cancer after progression on standard therapy.

Gastrointestinal Cancer - August 13, 2015

Bevacizumab Wins Cost-Effectiveness Analysis in First-Line Metastatic Colorectal Cancer

An economic analysis of the landmark CALGB/SWOG 80405 study, which compared bevaciz­umab versus cetuximab in patients with metastatic colorectal cancer, declares bevacizumab the clear winner, as its total cost is $39,000 less than cetuximab. “Chemotherapy plus bevacizumab costs less and achieves very similar survival and quality-adjusted survival as chemotherapy plus [ Read More ]

Immunotherapy - August 13, 2015

Nivolumab Is Superior to Docetaxel as Second-Line Therapy for Patients with NSCLC

Immunotherapy with the programmed death-1 (PD-1) inhibitor nivolumab as second-line therapy prolonged survival in patients with nonsquamous non–small cell lung cancer (NSCLC) who had experienced disease progression with standard platinum-based therapy. The patients in the nivolumab group lived an average of 3 months longer compared with patients receiving docetaxel in [ Read More ]