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

Sandra P. D’Angelo, Matthias Hunger, Andrew S. Brohl, Paul Nghiem, Shailender Bhatia, Omid Hamid, Janice Mehnert, Patrick Terheyden, Kent C. Shih, Isaac Brownell, Céleste Lebbé, Karl D. Lewis, Gerald P. Linette, Michele Milella, Michael Schlichting, Meliessa H. Hennessy, Murtuza Bharmal

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)609-618
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume68
Issue number4
DOIs
StatePublished - Apr 2 2019

Fingerprint

Merkel Cell Carcinoma
Survival
Confidence Intervals
Therapeutics
Proportional Hazards Models
avelumab
Risk Reduction Behavior

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Keywords

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

Cite this

D’Angelo, Sandra P. ; Hunger, Matthias ; Brohl, Andrew S. ; Nghiem, Paul ; Bhatia, Shailender ; Hamid, Omid ; Mehnert, Janice ; Terheyden, Patrick ; Shih, Kent C. ; Brownell, Isaac ; Lebbé, Céleste ; Lewis, Karl D. ; Linette, Gerald P. ; Milella, Michele ; Schlichting, Michael ; Hennessy, Meliessa H. ; Bharmal, Murtuza. / Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma. In: Cancer Immunology, Immunotherapy. 2019 ; Vol. 68, No. 4. pp. 609-618.
@article{98788fbd613243f8968797eddf50eb5f,
title = "Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma",
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",
author = "D’Angelo, {Sandra P.} and Matthias Hunger and Brohl, {Andrew S.} and Paul Nghiem and Shailender Bhatia and Omid Hamid and Janice Mehnert and Patrick Terheyden and Shih, {Kent C.} and Isaac Brownell and C{\'e}leste Lebb{\'e} and Lewis, {Karl D.} and Linette, {Gerald P.} and Michele Milella and Michael Schlichting and Hennessy, {Meliessa H.} and Murtuza Bharmal",
year = "2019",
month = "4",
day = "2",
doi = "10.1007/s00262-018-02295-4",
language = "English (US)",
volume = "68",
pages = "609--618",
journal = "Cancer Immunology, Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "4",

}

D’Angelo, SP, Hunger, M, Brohl, AS, Nghiem, P, Bhatia, S, Hamid, O, Mehnert, J, Terheyden, P, Shih, KC, Brownell, I, Lebbé, C, Lewis, KD, Linette, GP, Milella, M, Schlichting, M, Hennessy, MH & Bharmal, M 2019, 'Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma', Cancer Immunology, Immunotherapy, vol. 68, no. 4, pp. 609-618. https://doi.org/10.1007/s00262-018-02295-4

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma. / D’Angelo, Sandra P.; Hunger, Matthias; Brohl, Andrew S.; Nghiem, Paul; Bhatia, Shailender; Hamid, Omid; Mehnert, Janice; Terheyden, Patrick; Shih, Kent C.; Brownell, Isaac; Lebbé, Céleste; Lewis, Karl D.; Linette, Gerald P.; Milella, Michele; Schlichting, Michael; Hennessy, Meliessa H.; Bharmal, Murtuza.

In: Cancer Immunology, Immunotherapy, Vol. 68, No. 4, 02.04.2019, p. 609-618.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma

AU - D’Angelo, Sandra P.

AU - Hunger, Matthias

AU - Brohl, Andrew S.

AU - Nghiem, Paul

AU - Bhatia, Shailender

AU - Hamid, Omid

AU - Mehnert, Janice

AU - Terheyden, Patrick

AU - Shih, Kent C.

AU - Brownell, Isaac

AU - Lebbé, Céleste

AU - Lewis, Karl D.

AU - Linette, Gerald P.

AU - Milella, Michele

AU - Schlichting, Michael

AU - Hennessy, Meliessa H.

AU - Bharmal, Murtuza

PY - 2019/4/2

Y1 - 2019/4/2

N2 - 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.

AB - 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.

KW - Avelumab

KW - Endpoint validation

KW - Merkel cell carcinoma

KW - Objective response

KW - Overall survival

KW - PD-L1

UR - http://www.scopus.com/inward/record.url?scp=85061214366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061214366&partnerID=8YFLogxK

U2 - 10.1007/s00262-018-02295-4

DO - 10.1007/s00262-018-02295-4

M3 - Article

C2 - 30721341

AN - SCOPUS:85061214366

VL - 68

SP - 609

EP - 618

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

SN - 0340-7004

IS - 4

ER -