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Cancer Immunol Immunother. 2019 Apr;68(4):609-618. doi: 10.1007/s00262-018-02295-4. Epub 2019 Feb 5.

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Author information

1
Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 300 East 66th Street, 12th Floor, New York, NY, 10065, USA. dangelos@mskcc.org.
2
Mapi (An ICON plc Company), Munich, Germany.
3
Moffitt Cancer Center, Tampa, FL, USA.
4
Division of Dermatology, Department of Medicine, Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
5
Division of Medical Oncology, Department of Medicine, Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
6
The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
7
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
8
University of Lübeck, Lübeck, Germany.
9
Tennessee Oncology, Nashville, TN, USA.
10
Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
11
Hôpital Saint-Louis, Paris, France.
12
University of Colorado Cancer Center, Anschutz, Aurora, CO, USA.
13
Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
14
IRCCS Regina Elena National Cancer Institute, Rome, Italy.
15
Merck KGaA, Darmstadt, Germany.
16
EMD Serono, Billerica, MA, USA.

Abstract

BACKGROUND:

Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1).

METHODS:

Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies.

RESULTS:

Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6-97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7-37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4-12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018-0.152)] compared with a nonresponse.

CONCLUSIONS:

Patients with OR by 7 or 13 weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance.

KEYWORDS:

Avelumab; Endpoint validation; Merkel cell carcinoma; Objective response; Overall survival; PD-L1

PMID:
30721341
PMCID:
PMC6447510
DOI:
10.1007/s00262-018-02295-4
[Indexed for MEDLINE]
Free PMC Article

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