Gastrointestinal Cancers Symposium

Gastrointestinal Cancers Symposium

Perspective from Afsaneh Barzi, MD, PhD
Perspective from Shikha Jain, MD, FACP
Source:

Lenz HJ, et al. Abstract 8. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 20-22, 2022; San Francisco.

Disclosures: Lenz reports consultant/advisory roles with and honoraria and/or travel, accommodations and expenses from Bayer, GlaxoSmithKline, Merck Serono, Roche and several other pharmaceutical companies.
January 27, 2022
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Nivolumab regimen misses PFS endpoint but shows promise in metastatic colorectal cancer

Perspective from Afsaneh Barzi, MD, PhD
Perspective from Shikha Jain, MD, FACP
Source:

Lenz HJ, et al. Abstract 8. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 20-22, 2022; San Francisco.

Disclosures: Lenz reports consultant/advisory roles with and honoraria and/or travel, accommodations and expenses from Bayer, GlaxoSmithKline, Merck Serono, Roche and several other pharmaceutical companies.
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First-line nivolumab plus standard of care chemotherapy failed to prolong 1-year PFS among patients with metastatic colorectal cancer, according to study results presented at ASCO Gastrointestinal Cancers Symposium.

However, findings from the phase 2/phase 3 CheckMate 9x8 trial showed the immune checkpoint inhibitor nivolumab (Opdivo, Bristol Myers Squibb) plus FOLFOX and bevacizumab (Avastin, Genentech) conferred higher PFS rates after 1 year compared with standard-of-care chemotherapy alone.

“Although the primary endpoint was not met, the PFS curves overlapped up until 1 year and then separated, showing better PFS rates in the nivolumab combination at 15 months and 18 months, and response rates were also higher with the nivolumab combination,” Heinz-Josef Lenz, MD, FACP, professor of medicine at USC Norris Comprehensive Cancer Center, told Healio.

Rationale

Nivolumab, an anti-PD-1-antibody, may increase antitumor activity when combined with standard-of-care first-line treatment for patients with metastatic colorectal cancer, according to Lenz.

“The addition of immunotherapy to chemotherapy showed some benefit in previous research,” he added. “We, therefore, wanted to see whether nivolumab combined with standard chemotherapy would benefit this patient population.”

Methods

The CheckMate 9x8 study included 195 patients with previously untreated, unresectable metastatic colorectal cancer.

Researchers randomly assigned patients to 240 mg nivolumab plus FOLFOX and bevacizumab every 2 weeks (n = 127) or standard of care (FOLFOX and bevacizumab) every 2 weeks (n = 68).

PFS served as the primary endpoint. Secondary endpoints included objective response rate, disease control rate, time to response, duration of response, OS and safety.

The nivolumab combination group had median follow-up of 23.7 months and median duration of treatment of 9.9 months compared with 23.2 months and 7.7 months for the standard-of-care group.

Key findings

Results showed median 1-year PFS of 11.9 months for both treatment groups (HR = 0.81; 95% CI, 0.53-1.23).

However, the nivolumab combination conferred a PFS rate at 15 months of 45% (95% CI, 35.4-54.8) compared with 21.5% (95% CI, 9.7-36.4) for standard of care. Moreover, the combination conferred an 18-month PFS rate of 28% (95% CI, 19-38.4) vs. 9% (95% CI, 2.4-21.8) for standard of care.

Researchers additionally observed an ORR of 60% and median duration of response of 12.9 months with the nivolumab combination compared with an ORR of 46% and median duration of response of 9.3 months with standard of care.

“Exploratory analyses further showed interesting findings of a benefit in patients with tumors that expressed CMS1 and CMS3, as well as tumors that expressed more than 2% CD8 cells,” Lenz said.

The nivolumab combination group had higher rates of grade 3 to grade 4 adverse events, but researchers found no new safety signals.

Implications

Heinz-Josef Lenz, MD, FACP
Heinz-Josef Lenz

“These [results] have no direct impact on clinical decision-making but raise important findings that a subgroup of patients benefit from the nivolumab combination with standard of care chemotherapy,” Lenz said. “We need to better understand what patient population benefits. This is the first time that CMS3 is identified in microsatellite-stable patients to demonstrate benefit for nivolumab plus chemotherapy and warrants further investigation and testing.”

For more information:

Heinz-Josef Lenz, MD, can be reached at USC Norris Comprehensive Cancer Center, 1520 San Pablo St., Los Angeles, CA 90033; email: lenz@med.usc.edu.