Suresh S. Ramalingam
CHICAGO — Higher tumor mutational burden appeared associated with greater response to treatment with nivolumab plus ipilimumab among patients with advanced non-small cell lung cancer, according to results from the CheckMate 568 study presented at American Association for Cancer Research Annual Meeting.
“Checkpoint inhibition is seen as the standard of care for NSCLC in the frontline setting as monotherapy and in combination with chemotherapy,” Suresh S. Ramalingam, MD, deputy director of Winship Cancer Institute of Emory University, said during his presentation.
“The combination of nivolumab and ipilimumab has demonstrated activity in the CheckMate 012 study,” he added. “Tumor mutational burden was shown to be an emerging, predictive biomarker for response to checkpoint inhibition.”
In the CheckMate 568 study, Ramalingam and colleagues studied 288 patients with chemotherapy-naive stage IV or recurrent stage IIIb NSCLC who received nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) for up to 2 years.
Researchers excluded patients with ALK or EGFR targetable mutations.
The investigators used Foundation One CDx (Foundation Medicine, Inc.) to assess tumor mutational burden.
Objective response as assessed by independent review served as the primary endpoint.
ORR by tumor mutational burden served as a secondary endpoint.
ORR was 30% for all treated patients with a minimum follow-up of 3 months.
Researchers analyzed response by PD-L1 expression. The analysis included 57 patients with PD-L1 expression less than 1%, and 17 patients with PD-L1 expression of 1% or higher.
Results showed a higher ORR among those with higher PD-L1 expression (41% vs. 15%).
ORR increased with higher tumor mutational burden. Researchers reported ORRs of:
- 9% for those with less than 5 mutations/megabase;
- 15% for those with less than 10 mutations/megabase;
- 44% for those with at least 10 mutations/megabase; and
- 39% for those with at least 15 mutations/megabase.
Receiver operating characteristic analysis of tumor mutational burden demonstrated the optimal classification performance at 10 mutations/megabase.
Patients with at least 10 mutations/megabase had longer median PFS (7.1 months vs. 2.6 months) and a higher likelihood of 6-month PFS (55% vs. 31%) than those with less than 10 mutations/megabase.
The safety profile appeared consistent with previous trials of nivolumab plus ipilimumab. No new safety signals were observed. – by Cassie Homer
Ramalingam S. Abstract CT078. Presented at American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.
Disclosures: Ramalingam reports serving on the scientific advisory board for AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, Lilly, Merck, Roche and Takeda, as well as consulting and receiving research support from Bristol-Myers Squibb. Please see the abstract for all other authors’ relevant financial disclosures.