ASCO Annual Meeting
ASCO Annual Meeting
Perspective from Mark O’Hara, MD
Perspective from Michael Overman, MD
Source/Disclosures
Source:

Andre T, et al. Abstract LBA4. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.

Disclosures: Merck funded this study. Andre reports honoraria from, consultant/advisory roles with, or travel, accommodations or expenses from Amgen, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Clovis Oncology, GIC Advice, HalioDX, Genentech/Roche, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, Tesaro and Vantana. Please see the abstract for all other researchers’ relevant financial disclosures.
May 29, 2020
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Pembrolizumab doubles PFS for certain patients with metastatic colorectal cancer

Perspective from Mark O’Hara, MD
Perspective from Michael Overman, MD
Source/Disclosures
Source:

Andre T, et al. Abstract LBA4. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.

Disclosures: Merck funded this study. Andre reports honoraria from, consultant/advisory roles with, or travel, accommodations or expenses from Amgen, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Clovis Oncology, GIC Advice, HalioDX, Genentech/Roche, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, Tesaro and Vantana. Please see the abstract for all other researchers’ relevant financial disclosures.
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First-line pembrolizumab extended PFS vs. chemotherapy for patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer, according to findings to be presented during the ASCO20 Virtual Scientific Program.

The agent also appeared associated with fewer treatment-related adverse events.

“Pembrolizumab should be considered a new standard of care for these patients,” Thierry André, MD, professor of medical oncology at University Sorbonne and head of the medical oncology department at Hôpital Saint Antoine in Paris, said during a presentation. “These data represent another step forward for biomarker-driven studies and will help bring this approach to target microsatellite instability-high tumors into the adjuvant and neoadjuvant settings.”

An estimated 5% of patients with metastatic colorectal cancer have high microsatellite instability, characterized by a high level of mutations.

First-line pembrolizumab extended PFS vs. chemotherapy for patients with microsatellite instability-high, mismatch repair-deficient metastatic colorectal cancer.

In microsatellite instability-high/mismatch repair-deficient disease, DNA repair is compromised, leading to an even higher number of mutations. This subgroup of patients is less likely to respond to conventional chemotherapy and, therefore, prognosis typically is poor.

Phase 2 studies showed pembrolizumab improved response and prolonged survival for patients with microsatellite instability-high metastatic colorectal cancer refractory to chemotherapy. The FDA approved pembrolizumab for treatment of adults and children with previously treated microsatellite instability-high metastatic tumors regardless of tumor type or site.

The randomized, phase 3 KEYNOTE-177 trial assessed the efficacy and safety of the anti-PD-1 therapy pembrolizumab (Keytruda, Merck) vs. standard chemotherapy as first-line treatment for patients with microsatellite instability-high, mismatch repair-deficient metastatic colorectal cancer.

All 307 patients had measurable disease and an ECOG performance status of 0 or 1.

Researchers randomly assigned 153 patients to pembrolizumab dosed at 200 mg every 3 weeks. The other 154 patients received investigator’s choice of one of six standard chemotherapy regimens selected prior to randomization. These included modified FOLFOX-6, which consists of 5-FU, leucovorin and oxaliplatin; modified FOLFOX-6 plus bevacizumab (Avastin, Genentech); modified FOLFOX-6 plus cetuximab (Erbitux, Eli Lilly); FOLFIRI, which consists of leucovorin, 5-FU and irinotecan; FOLFIRI plus bevacizumab; or FOLFIRI plus cetuximab.

Treatment continued until disease progression, unacceptable toxicity, patient or investigator decision to withdraw, or — in the case of pembrolizumab — completion of 35 cycles. Patients assigned chemotherapy who developed confirmed progressive disease could cross over to pembrolizumab for up to 35 cycles.

PFS by blinded independent central review and OS served as primary endpoints. Key secondary endpoints included overall response rate and safety.

André presented results of the final PFS analysis, based on median follow-up of 32.4 months (range, 24-48.3).

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Results showed a near-doubling of median PFS with pembrolizumab (16.5 months vs. 8.2 months; HR = 0.6; 95% CI, 0.45-0.8). A higher percentage of patients assigned pembrolizumab remained progression free at 12 months (55.3% vs. 37.3%) and 24 months (48.3% vs. 18.6%).

Researchers also reported a higher ORR in the pembrolizumab group (43.8% vs. 33.1%), as well as higher rates of complete response (11.1% vs. 3.9%) and partial response (32.7% vs. 29.2%).

Median response duration was not reached with pembrolizumab (range, 2.3+ months to 41.4+ months) and was 10.6 months (range, 2.8-37.5+) with chemotherapy. More than twice as many patients assigned pembrolizumab remained in response for 2 years or longer (83% vs. 35%).

The majority of patients in each group experienced treatment-related adverse events (80% for pembrolizumab vs. 99% for chemotherapy). However, a considerably lower percentage of patients assigned pembrolizumab experienced grade 3 to grade 5 treatment-related adverse events (22% vs. 66%).

The most common adverse events reported among pembrolizumab-treated patients included diarrhea (any grade, 25% for pembrolizumab vs. 52% for chemotherapy; grade 3 or higher, 2% vs. 10%), fatigue (any grade, 21% vs. 44%; grade 3 or higher, 2% vs. 9%), nausea (any grade, 12% vs. 55%; grade 3 or higher, 0% vs. 2%), decreased appetite (any grade, 8% vs. 34%; grade 3 or higher, 0% vs. 2%) and stomatitis (any grade, 5% vs. 30%; grade 3 or higher, 0% vs. 4%).

One patient assigned chemotherapy died due to a treatment-related adverse event.

The study will continue so researchers can assess OS outcomes.

“Our hope is that after starting pembrolizumab, some patients will be cured of metastatic disease,” André said. – by Mark Leiser

Reference:

Andre T, et al. Abstract LBA4. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.

Disclosure: Merck funded this study. Andre reports honoraria from, consultant/advisory roles with, or travel, accommodations or expenses from Amgen, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Clovis Oncology, GIC Advice, HalioDX, Genentech/Roche, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, Tesaro and Vantana. Please see the abstract for all other researchers’ relevant financial disclosures.