Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006

Omid Hamid; Caroline Robert; Adil Daud; Matteo S Carlino; Tara C Mitchell; Peter Hersey; Jacob Schachter; Georgina V Long; F Stephen Hodi; Jedd D Wolchok; Ana Arance; Jean Jacques Grob; Anthony M Joshua; Jeffrey S Weber; Laurent Mortier; Erin Jensen; Scott J Diede; Blanca Homet Moreno; Antoni Ribas

doi:10.1016/j.ejca.2021.08.013

Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006

Eur J Cancer. 2021 Nov:157:391-402. doi: 10.1016/j.ejca.2021.08.013. Epub 2021 Sep 25.

Authors

Omid Hamid¹, Caroline Robert², Adil Daud³, Matteo S Carlino⁴, Tara C Mitchell⁵, Peter Hersey⁶, Jacob Schachter⁷, Georgina V Long⁸, F Stephen Hodi⁹, Jedd D Wolchok¹⁰, Ana Arance¹¹, Jean Jacques Grob¹², Anthony M Joshua¹³, Jeffrey S Weber¹⁴, Laurent Mortier¹⁵, Erin Jensen¹⁶, Scott J Diede¹⁷, Blanca Homet Moreno¹⁸, Antoni Ribas¹⁹

Affiliations

¹ Department of Oncology, The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, 11818 Wilshire Blvd, Los Angeles, CA 90025, USA. Electronic address: [email protected].
² Department of Oncology, Service of Dermatology, Gustave Roussy, 114 Rue Edouard Vaillant 94805, Villejuif, France; Paris-Saclay University, 15, Rue Georges Clemenceau 91400, Orsay, France. Electronic address: [email protected].
³ Department of Hematology/Oncology, University of California San Francisco, 1600 Divisadero St, San Francisco, CA 94115, USA. Electronic address: [email protected].
⁴ The Crown Princess Mary Cancer Centre Westmead, Westmead Hospital, and Blacktown and Mount Druitt Hospital, 166-174 Hawkesbury Rd, Westmead, NSW 2145, Australia; Melanoma Institute Australia, Faculty of Medicine and Health, University of Sydney, 40 Rocklands Rd, Sydney, NSW 2065, Australia. Electronic address: [email protected].
⁵ Division of Hematology and Oncology, Abramson Cancer Center, Penn Medicine, 3400 Civic Center Blvd, South Pavilion, Floor 10, Philadelphia, PA 19104, USA. Electronic address: [email protected].
⁶ Department of Medicine, University of Sydney, Edward Ford Building A27, Sydney, NSW 2006, Australia. Electronic address: [email protected].
⁷ The Chaim Sheba Medical Center at Tel HaShomer, Tel HaShomer, Sheba Medical Center, Tel HaShomer Hospital, Ramat Gan 52621, Israel. Electronic address: [email protected].
⁸ Melanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, North Sydney, NSW 2040, Australia; Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia; Charles Perkins Centre, The University of Sydney, NSW 2006, Australia; Royal North Shore & Mater Hospitals, Pacific Highway, St. Leonards, NSW 2065, Australia. Electronic address: [email protected].
⁹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address: [email protected].
¹⁰ Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. Electronic address: [email protected].
¹¹ Department of Medical Oncology, Hospital Clinic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Electronic address: [email protected].
¹² Department of Dermatology and Skin Cancers, Aix Marseille University, Hôpital de la Timone, 264 Rue Saint Pierre 13005, Marseille, France. Electronic address: [email protected].
¹³ Department of Medical Oncology, UHN Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2C1, Canada; The Kinghorn Cancer Centre at St Vincent's Hospital, 370 Victoria St, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Sydney, 390 Victoria St, Darlinghurst, NSW 2010, Australia; Melanoma Institute Australia, 40 Rocklands Rd, North Sydney, NSW 2065, Australia. Electronic address: [email protected].
¹⁴ Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, 522 First Avenue, Room 1310 Smilow Bldg, New York, NY 10016, USA. Electronic address: [email protected].
¹⁵ Department of Dermatology, Lille University, INSERM U1189, 2, Avenue Oscar Lambret 59037, Lille, France. Electronic address: [email protected].
¹⁶ Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: [email protected].
¹⁷ Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: [email protected].
¹⁸ Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: [email protected].
¹⁹ Department of Medicine, Jonsson Comprehensive Cancer Center and David Geffen School of Medicine, University of California Los Angeles, 100 Medical Plaza Driveway #550, Los Angeles, CA 90095, USA. Electronic address: [email protected].

Abstract

Objective: Patients with melanoma and early stable disease (SD) with pembrolizumab have unclear prognosis. We present post hoc analyses of long-term outcomes for patients with early SD, partial response (PR) or complete response (CR) with pembrolizumab.

Patients and methods: Patients who received pembrolizumab in the KEYNOTE-001 and KEYNOTE-006 studies and had SD, PR or CR at weeks 12 or 24 were included.

Results: Of 294 patients in the week 12 analysis, 107 (36.4%) had SD at week 12, of whom 7 (6.5%) had a best overall response of CR, 43 (40.2%) had PR and 57 (53.3%) had SD. Forty-eight-month overall survival (OS) rates were 95.2%, 73.0% and 47.7%, respectively, for patients with CR, PR and SD at week 12. Similar results were observed in the 241 patients in the week 24 analysis. Forty-eight-month OS rates were 72.1% for patients with SD at week 12 followed by subsequent response and 75.0% for patients with PR at week 12 followed by no change in response or progression. Thirty-six-month and 48-month OS rates were 11.6% and not reached, respectively, for patients with SD at week 12 followed by progression before week 24.

Conclusions: A substantial proportion of patients (46.7%) with early (week 12) SD with pembrolizumab achieved subsequent PR or CR. Patients with SD at week 12 and subsequent CR/PR had similar survival to those who maintained PR. In contrast, patients with SD at week 12 and subsequent progression had poor survival outcomes. These findings may guide treatment decisions for patients achieving early SD.

Trial registration: Clinicaltrials.gov: NCT01295827 (KEYNOTE-001); NCT01866319 (KEYNOTE-006).

Keywords: Melanoma; PD-1; Pembrolizumab; Programmed death 1.

Publication types

Clinical Trial, Phase I
Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies, Monoclonal, Humanized / administration & dosage*
Antibodies, Monoclonal, Humanized / adverse effects
Clinical Decision-Making
Disease Progression
Drug Administration Schedule
Female
Humans
Immune Checkpoint Inhibitors / administration & dosage*
Immune Checkpoint Inhibitors / adverse effects
Male
Melanoma / diagnosis
Melanoma / drug therapy*
Melanoma / mortality
Middle Aged
Neoplasm Staging
Patient Selection
Prognosis
Progression-Free Survival
Skin Neoplasms / diagnosis
Skin Neoplasms / drug therapy*
Skin Neoplasms / mortality
Survival Rate

Substances

Antibodies, Monoclonal, Humanized
Immune Checkpoint Inhibitors
pembrolizumab

Associated data

ClinicalTrials.gov/NCT01295827
ClinicalTrials.gov/NCT01866319

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States