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PD-L1 expression predicted response to immunotherapy in melanoma

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NEW YORK — Patients with advanced melanoma whose tumors expressed programmed death ligand-1 demonstrated higher rates of overall response and disease control than patients whose tumors were PD-L1 negative, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

PD-L1 expression also was associated with significantly improved PFS, although researchers did not observe a significant difference in OS.

The binding of PD-1 — a protein present on T cells — with the PD-L1 protein present on some melanoma tumors prevents T cells from attacking cancer cells. MK-3475 (Merck) — a humanized, monoclonal IgG4 antibody — is designed to block PD-1, allowing the T cells to attack cancer cells.

 

Adil I. Daud

Adil I. Daud, MD, co-director of the UCSF Melanoma Center and director of melanoma clinical research at the UCSF Helen Diller Family Comprehensive Cancer Center, and colleagues evaluated tumor samples from 125 patients (median age, 63 years) with late-stage melanoma.

Some patients had undergone prior treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol-Myers Squibb). Those who had not undergone prior ipilimumab were only eligible if they had undergone two or fewer prior therapies.

All patients had ECOG performance status of 0 (73%) or 1 (27%). Patients on systemic steroids, those with active autoimmune disease, and those with active or untreated CNS metastases were excluded.

Of the 125 tumor samples, 89 (71.2%) were PD-L1 positive, meaning at least one of every 100 tumor cells expressed the protein. The other 36 samples were PD-L1 negative.

All patients had at least 6 months of follow-up, and 75% of patients had at least 9 months of follow-up.

The majority of patients (67%) experienced a reduction in tumor size during treatment with MK-3475, and researchers reported a 40% overall response rate in unselected patients.

Patients with PD-L1–positive tumors demonstrated higher rates of overall response (49% vs. 13%; P=.0007) and disease control (65% vs. 37%; P=.007).

Patients with PD-L1–positive tumors experienced significantly longer median PFS (10.6 months. vs. 2.9 months; HR=0.52; 95% CI, 0.32-0.86), as well as higher rates of 6-month PFS (57% vs. 35%) and 12-month PFS (45% vs. 18%).

Although median OS was not reached, researchers calculated an HR of 0.83 (95% CI, 0.39-1.78) in favor of patients with PD-L1–positive tumors. The difference in OS between groups was not statistically significant.

Researchers reported 6-month OS rates of 91% for patients with PD-L1–positive tumors and 79% for patients with PD-L1–negative tumors.

Among all patients, researchers reported significant median increases in the percentage of CD4-positive T cells and CD8-positive T cells between baseline to week 6 of treatment (P<.001 for both). However, there was no significant change in the absolute number of circulating T cells, Daud and colleagues wrote.

For more information:

Daud AI. Antitumor activity of the anti-PD-1 monoclonal antibody MK-3475 in melanoma: Correlation of tumor PD-L1 expression with outcome. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 11-12, 2014; New York.

Disclosure: The study was funded by Merck. Daud reports research support from Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck and Pfizer, as well as advisory board roles with Merck and GlaxoSmithKline.