VOLUME 35 • NUMBER 36 • DECEMBER 20, 2017

JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T

Safety and Efficacy of Pembrolizumab in Advanced,

Programmed Death Ligand 1–Positive Cervical Cancer:
Results From the Phase Ib KEYNOTE-028 Trial
Jean-Sebastien Frenel, Christophe Le Tourneau, Bert O’Neil, Patrick A. Ott, Sarina A. Piha-Paul, Carlos
Gomez-Roca, Emilie M.J. van Brummelen, Hope S. Rugo, Shari Thomas, Sanatan Saraf, Reshma Rangwala, and
Andrea Varga

Author affiliations and support information

(if applicable) appear at the end of this A B S T R A C T
article.
Purpose
Published at jco.org on November 2,
2017.
The KEYNOTE-028 trial (ClinicalTrials.gov identifier: NCT02054806) was designed to assess the
safety and efficacy of pembrolizumab in 20 programmed death ligand 1–positive, advanced solid
Clinical trial information: NCT02054806.
tumor cohorts. Here, we present the results from the cohort of patients with advanced cervical
Corresponding author: Jean-Sebastien cancer.
Frenel, MD, Institut de Cancerologie de
l’Ouest, Centre Rene Gauducheau, Methods
11 Blvd Jacques Monod, 44800 Patients were treated with pembrolizumab 10 mg/kg every 2 weeks for up to 24 months. Response
Saint-Herblain, France; e-mail:
was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary end
Jean-Sebastien.Frenel@ico.unicancer.fr.
point was overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, by
© 2017 by American Society of Clinical
investigator review. Safety was a secondary end point.
Oncology

0732-183X/17/3536w-4035w/$20.00
Results
Twenty-four patients were enrolled in the cervical cancer cohort. The median age was 42 years
(range, 26 to 62 years), 22 patients (92%) had received prior radiation therapy, and 15 patients (63%)
had received two or more lines of therapy, including bevacizumab (10 of 24 patients), for advanced
disease. At the data cutoff, median follow-up duration was 11.0 months (range, 1.3 to 32.2 months).
Overall response rate was 17% (95% CI, 5% to 37%); four patients (17%) achieved a confirmed
partial response, and three patients (13%) had stable disease. Median duration of response for the
four patients who achieved a partial response was 5.4 months (4.1 to 7.5 months). Treatment related
adverse events (AEs) were experienced by 18 patients (75%); only rash (n = 5; 21%) and pyrexia
(n = 4; 17%) and occurred in $ 10% of patients. Five patients experienced grade 3 treatment-related
AEs. No grade 4 treatment-related AEs or deaths were observed.
Conclusion
In patients with programmed death ligand 1–positive advanced cervical cancer, pembrolizumab
demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other
tumor types.

J Clin Oncol 35:4035-4041. © 2017 by American Society of Clinical Oncology

In the United States, 46% of patients di-

INTRODUCTION
Although the use of screening programs and the
introduction of vaccines protecting against the
human papillomavirus (HPV) have dramatically
reduced the incidence of cervical cancer, the
ASSOCIATED CONTENT
disease remains a problem in populations without
access to adequate health care.1 Consequently,
Data Supplement
DOI: https://doi.org/10.1200/JCO.
cervical cancer is the second most commonly
2017.74.5471 diagnosed malignancy in women in the de-
DOI: https://doi.org/10.1200/JCO.2017. veloping world, with 87% of all cervical cancer
74.5471 deaths occurring in developing regions.1,2
agnosed with cervical cancer will present with
localized disease.3 The prognosis for these pa-
tients is good, with a 5-year survival rate of 91%.4
In contrast, the prognosis for patients with ad-
vanced disease is poor, with a 5-year survival rate
of only 17%.4,5 For recurrent or metastatic dis-
ease, cisplatin-based therapy has been a common
treatment option5-7; however, outcomes are dis-
appointing, with response rates ranging from
13% with cisplatin alone to 36% with cisplatin-
containing doublet therapy.8-10 Recently, bev-
acizumab in combination with chemotherapy

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Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
 Frenel et al
compared with chemotherapy alone was found to provide an
overall survival (OS) advantage (17 months v 13 months) and
a higher response rate (48% v 36%).11 However, after progression,
only limited treatment options exist, including single-agent ther-
apies and palliative care.5-7
Programmed death 1 (PD-1) is a T-cell coinhibitory recep-
tor that under normal conditions functions in an immuno-
regulatory manner.12 PD-1 is known to play a significant role
in cancer by contributing to the ability of a tumor to avoid
immunosurveillance. 13,14 Pembrolizumab is a highly selective,
fully humanized monoclonal antibody that prevents the in-
teraction between PD-1 and its ligands, programmed death
ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2).15,16
Pembrolizumab is currently approved for the treatment of
melanoma in more than 60 countries, in the United States and
Europe for metastatic non–small-cell lung cancer, urothelial
carcinoma, and adults with relapsed/refractory classic Hodgkin
lymphoma, and in the United States for recurrent or metastatic
head and neck squamous cell carcinoma (HNSCC), pediatric
patients with relapsed/refractory classic Hodgkin lymphoma,
and microsatellite instability high or mismatch repair deficient
cancer.15,17 The recent identification of PD-L1 expression in
cervical intraepithelial neoplasias and cervical cancers suggests
that PD-1 may be an attractive therapeutic target for patients
with advanced cervical malignancies.18,19 Pembrolizumab is
currently under investigation as a treatment of PD-L1–positive
solid tumors in the phase Ib KEYNOTE-028 trial (ClinicalTrials.
gov indentifier: NCT02054806). Here, we report the results from the
cervical cancer cohort.
METHODS
Study Design and Patient Population
KEYNOTE-028 (Data Supplement) is a multicenter, phase Ib, single-
arm trial investigating the safety and efficacy of pembrolizumab in 20
different PD-L1–positive advanced solid tumors. Within this report, we
present results from the cohort of patients with advanced cervical cancer.
Informed consent was obtained for all patients, and the trial was conducted
in compliance with local and national regulations and in accordance with
the ethical principles that have their origin in the Declaration of Helsinki.
Patients were required to be $ 18 years of age and have histologically
or cytologically documented, locally advanced, or metastatic PD-L1–
positive cervical cancer that had progressed after prior standard therapy,
for which no standard therapy existed, or for whom standard therapy was
not considered appropriate. PD-L1 positivity, determined using an ar-
chived formalin-fixed paraffin-embedded tumor sample or newly obtained
core or excisional biopsy sample, was defined as membranous staining
on $ 1% modified proportion score or interface pattern as assessed using
a laboratory-developed prototype immunohistochemistry assay (QualTek
Molecular Laboratories, Goleta, CA)20 and the 22C3 antibody (Merck &
Co., Inc., Kenilworth, NJ).21 Additional eligibility criteria included mea-
surable disease per Response Evaluation Criteria in Solid Tumors, version 1.1
(RECIST v1.1); Eastern Cooperative Oncology Group performance status
of 0 or 1; and adequate organ function. Patients were excluded if they had
received chemotherapy, targeted small molecule therapy, or radiation
therapy within 2 weeks before treatment initiation; if they had received
a prior anticancer monoclonal antibody or any investigational agent within
4 weeks before treatment initiation; or if they had previously received any
anti–PD-1, anti–PD-L1, or anti–PD-L2 therapy. Patients with an active
infection requiring systemic therapy, evidence of interstitial lung disease,
4036 © 2017 by American Society of Clinical Oncology
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a diagnosis of immunodeficiency, known additional malignancies, active
central nervous system metastases, or an active autoimmune disease re-
quiring systemic treatment within the past 2 years were also excluded.
Treatment and Assessments
Patients received pembrolizumab 10 mg/kg as a 30-minute in-
travenous infusion every 2 weeks. Treatment was continued for up to
24 months or until withdrawal of consent, confirmed radiographic pro-
gression, unacceptable toxicity, or investigator decision. Participants with
stable disease (SD) or better on treatment discontinuation could be eligible
to restart pembrolizumab treatment of up to 1 year if they exhibited
subsequent disease progression. Treatment could be withheld for patients
exhibiting intolerable or persistent grade 2 treatment-related adverse
events (AEs) and was permanently discontinued if the toxicity did not
resolve to grade 0 to 1 within 12 weeks.
Safety was monitored throughout the study and for 30 days after
treatment discontinuation (90 days for serious AEs and immune-mediated
AEs). AEs were graded according to the National Cancer Institute
Common Terminology Criteria for Adverse Events (version 4.0). Immune-
mediated AEs were defined as events with potentially drug-related im-
munologic causes that were consistent with an immune phenomenon,
regardless of attribution to treatment or immune relatedness by the in-
vestigator. Response was assessed by computed tomography or magnetic
resonance imaging every 8 weeks for the first 6 months, and every 12 weeks
thereafter. If radiologic imaging indicated progressive disease, a repeat
assessment was required $ 4 weeks later. If the follow-up scan confirmed
progression, treatment was discontinued. Patients were given the option to
continue treatment until progression was confirmed.
End Points
The primary end point was overall response rate (ORR). ORR was
defined as the proportion of patients achieving either a confirmed complete
response or partial response (PR), per RECIST v1.1, by investigator review.
Secondary end points included safety and tolerability, progression-free
survival (PFS; time from allocation to first documented disease progression
according to RECIST v1.1 or death from any cause), OS (time from en-
rollment to death from any cause), and duration of response (DOR; time
from first observation of response according to RECIST v1.1 to radio-
graphic disease progression in patients who had achieved PR or better).
Statistical Analyses
A sequential monitoring procedure was used to evaluate efficacy and
futility after at least six patients had at least one postbaseline response
assessment. Enrollment continued provided at least one of the first six
patients exhibited a response. A sample size of 22 patients per cohort was
calculated using the binomial exact method to provide 80% power to
demonstrate that the best ORR induced by pembrolizumab exceeded 10%
at an overall one-sided 8% a level, if the true best ORR was 35%. For ORR,
the point estimate, repeated CI, and adjusted P value for testing whether
the RECIST v1.1 response rate was greater than 10% was provided using
a truncated sequential probability ratio test. DOR, PFS, and OS were
estimated using the Kaplan-Meier method. Efficacy was assessed in all
patients who had measurable disease at baseline per RECIST v1.1 and who
received at least one dose of pembrolizumab. Safety, analyzed using de-
scriptive statistics, was assessed in all patients who received at least one dose
of pembrolizumab. The data cutoff for this analysis was February 20, 2017.
RESULTS
Baseline Patient Characteristics
Of the 46 patients with cervical cancer who were screened, 39
were PD-L1 positive and 24 were ultimately enrolled in the study
JOURNAL OF CLINICAL ONCOLOGY
 Efficacy of Pembrolizumab in PD-L1–Positive Cervical Cancers

18 patients, with only rash (n = 5; 21%) and pyrexia (n = 4; 17%)

Patients screened for PD-L1 occurring in $ 10% of patients (Table 2). Grade 3 treatment-
(N = 46) related AEs were experienced by five patients and included neu-
tropenia, rash, colitis, Guillain-Barré syndrome, and proteinuria.
No grade 4 treatment-related AEs were observed, and no
Nonevaluable
treatment-related deaths occurred. Four patients (17%) experi-
Inadequate tumor sample (n = 1)
enced serious AEs that were considered treatment related, which
included one case each of rash (grade 3), colitis (grade 3), Guillain-
Samples evaluable for PD-L1 Barré syndrome (grade 3), and pyrexia (grade 2). Two patients
(n = 45) discontinued treatment because of grade 3 treatment-related AEs
(colitis and Guillain-Barré syndrome). After discontinuation, the
patient with Guillain-Barré syndrome received tegeline and re-
Patients positive for PD-L1 covered. Immune-mediated AEs were observed in six patients and
(n = 39)
included rash (n = 2; grade 3), colitis (n = 1; grade 3), Guillain-
Barré syndrome (n = 1; grade 3), hyperthyroidism (n = 1; grade 2),
and hypothyroidism (n = 1; grade 2).
Reasons for exclusion
No informed consent (n = 2)*
ECOG PS ineligible (n = 6)
Received prior chemotherapy, (n = 1) Antitumor Activity
targeted small molecule ORR was 17% (95% CI, 5% to 37%; n = 4) on the basis of
therapy, or radiation therapy
within 2 weeks before study
RECIST v1.1 by investigator review, with four patients (17%; 95%
day 1 or had not recovered CI, 5% to 37%) achieving a confirmed PR (Table 3). In these four
(ie, ≤ grade 1 or at baseline)
from AEs due to a previously
administered agent
Stratification cap met (n = 6)
Table 1. Baseline Characteristics
Total
Patients treated as of (N = 24) Characteristic (N = 24)
February 20, 2017
Median age, years (range) 42 (26-62)
Discontinued (n = 24)
AE (n = 4) Race
Physician decision (n = 1) White 15 (63)
Progressive disease (n = 19) Asian 1 (4)
Not specified 8 (33)
ECOG PS
Fig 1. CONSORT diagram of patient disposition. (*)One patient from this group 0 6 (25)
was also excluded due to receiving chemotherapy within 2 weeks before study 1 18 (75)
entry. AEs, adverse events; ECOG PS, Eastern Cooperative Oncology Group Histology
performance status; PD-L1, programmed death ligand 1. Squamous cell carcinoma 23 (96)
Adenocarcinoma 1 (4)
Metastatic stage
(Fig 1); these 24 patients had a median age of 42 years (range, 26 to MX 1 (4)
62 years; Table 1). All patients (n = 24; 100%) presented with M0 6 (25)
M1 15 (63)
metastatic disease, which was most frequently located in the lymph Unknown 2 (8)
nodes (n = 16; 67%), lung (n = 9; 38%), pelvis (n = 9; 38%), and Location of metastases
liver (n = 6; 25%). Patients were pretreated, with 92% (n = 22) Lymph node 16 (67)
having received prior radiation therapy and 63% (n = 15) having Lung 9 (38)
Pelvis 9 (38)
received two or more lines of chemotherapy for advanced disease. Liver 6 (25)
All but one patient had received platinum-based chemotherapy Bone 5 (21)
before study start, and 10 of 24 patients (42%) had received prior Pleural cavity 3 (13)
Bladder 2 (8)
bevacizumab. All patients discontinued treatment during the study,
Retroperitoneum 2 (8)
four (17%) because of AEs, one (4%) because of physician decision, Other 11 (46)
and 19 (79%) because of progressive disease (Fig 1). Among the Prior radiotherapy 22 (92)
24 PD-L1–positive patients enrolled in this cohort, 18 (75%) were Prior lines of therapy for advanced disease
1 9 (38)
PD-L1 positive in the tumor only and six (25%) were positive in 2 6 (25)
the tumor and stroma. $3 9 (38)
Prior platinum 23 (96)
Prior bevacizumab 10 (42)
Safety
NOTE. Data presented as No. (%) unless otherwise indicated.
At the time of the data cutoff, median follow-up duration was Abbreviation: ECOG PS, Eastern Cooperative Oncology Group performance
11.0 months (range, 1.3 to 32.2 months). AEs considered related status.
to the study drug (treatment-related AEs) were observed in

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 Frenel et al

Table 2. Treatment-Related Adverse Events of Any Grade Observed in Two or More Patients (N = 24)
Treatment-Related Adverse Event Grade 1, No. (%) Grade 2, No. (%) Grade 3, No. (%) Total, No. (%)*
Any 6 (25) 7 (29) 5 (21) 18 (75)
Rash† 3 (13) 0 (0) 2 (8) 5 (21)
Pyrexia 2 (8) 2 (8) 0 (0) 4 (17)
Fatigue 1 (4) 1 (4) 0 (0) 2 (8)
Asthenia 1 (4) 1 (4) 0 (0) 2 (8)
Constipation 1 (4) 1 (4) 0 (0) 2 (8)
Diarrhea 2 (8) 0 (0) 0 (0) 2 (8)
Dry mouth 2 (8) 0 (0) 0 (0) 2 (8)
Anemia 1 (4) 1 (4) 0 (0) 2 (8)
Proteinuria 1 (4) 0 (0) 1 (4) 2 (8)
Dry skin 2 (8) 0 (0) 0 (0) 2 (8)
Pruritus 2 (8) 0 (0) 0 (0) 2 (8)

NOTE. Included patients who had received one or more doses of pembrolizumab.
*Only the highest-grade adverse event was counted.
†Includes rash, macular rash, and maculopapular rash.

patients, the predominant site of responding disease was the lymph

nodes in all four patients (not in a previously radiated field), cervix
uteri in one patient (who received prior radiation to the pelvis),
and the lungs and liver in one patient. Three patients had SD (13%;
95% CI, 3% to 32%), and 16 patients had progressive disease (67%;
95% CI, 45% to 84%) as best response. Median time to response in
the four patients who achieved PR was 1.9 months (range, 1.7 to
8.2 months), and median DOR for responders was 5.4 months
(range, 4.1 to 7.5 months; Fig 2A). Two of the four patients
achieving PR exhibited a response for over 6 months. Tumor
samples from all four patients with PRs had PD-L1 expression in
the tumor only.
A decrease in the sum of diameters of target lesions from
baseline was observed in 8 (36%) of 22 evaluable patients by
computed tomography scan (Fig 2B); these decreases in patients
with PRs were maintained over time (Fig 2C). Median PFS in all
patients was 2 months (95% CI, 2 to 3 months), the PFS rate at
6 months was 21%, and the PFS rate at 12 months was 4% (Fig 3A).
Median OS in all patients was 11 months (95% CI, 4 to 15 months),
and the OS rate at 6 and 12 months was 67% and 40%, respectively
(Fig 3B).
Table 3. Best Overall Response as Assessed by Investigator Review
According to RECIST v1.1 (N = 24)
Best Overall Response No. % (95% CI)
Partial response* 4 17
Stable disease 3 13
Progressive disease 16 67
No assessment† 1 4
NOTE. Only confirmed responses were included. Patients who received one or
more doses of pembrolizumab and had measurable disease at baseline as per
RECIST v1.1 were included.
Abbreviation: RECIST v1.1, Response Evaluation Criteria in Solid Tumors ver-
sion 1.1.
*There were no complete responses.
†Patient was treated but had no postbaseline response evaluation because that
patient discontinued the treatment as a result of an adverse event before the
scan.
DISCUSSION
The results from the phase Ib KEYNOTE-028 trial presented herein
suggest that pembrolizumab has promising antitumor activity in
PD-L1–positive advanced cervical cancer. The ORR in this pop-
ulation was 17%, with four patients achieving PR and an additional
three patients exhibiting SD. Of note, one patient did respond on
a previously irradiated site. A median OS of 11 months and
a 6-month OS rate of 67% further indicate the potential of
pembrolizumab for treating advanced cervical cancer. The safety
profile for pembrolizumab was consistent with that seen in other
tumor types,16 with two patients discontinuing treatment be-
cause of grade 3 treatment-related AEs, and no grade 4 treatment-
related AEs or treatment-related mortality occurred.
Cisplatin is widely recognized as the primary treatment of
patients with advanced cervical cancer, either in combination with
radiotherapy or as a first-line option for patients with disease that is
not amenable to local treatment.6 However, the efficacy of cisplatin-
based regimens is limited, and toxicity remains a concern.8-10
Furthermore, many patients with advanced cervical cancer have
previously received cisplatin as treatment of primary disease and
may have developed resistance to platinum-based chemotherapy.22
Several single-arm, phase II clinical trials evaluating the treatment of
advanced cervical cancer in the second-line setting have been
previously conducted by the Gynecologic Oncology Group.23-33
ORRs in these studies ranged from 0% to 19%,23-33 with only
three regimens providing an ORR of . 10% (topotecan, vinorelbine,
and bevacizumab).24,26,31 In addition, only three regimens (oxali-
(5 to 37) platin, cisplatin plus pentoxifylline, and bevacizumab) were asso-
(3 to 32)
(45 to 84) ciated with 6-month PFS rates of . 20%.23,25,31 Taken together,
(, 1 to 21) these findings further support the promising antitumor activity of
pembrolizumab in the current study, which was associated with an
ORR of 17% and a 6-month PFS rate of 21%.
The most significant shift in the treatment paradigm for
advanced cervical cancer has been the recent inclusion of bev-
acizumab as part of first-line chemotherapy combinations.6 The
addition of the antivascular endothelial growth factor antibody to
treatment guidelines was based on the results of the Gynecologic
Oncology Group 240 trial, in which the addition of bevacizumab to

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 Efficacy of Pembrolizumab in PD-L1–Positive Cervical Cancers

A C
100

80
Nonresponder
60 Responder

Change From Baseline (%)

40
+20% Tumor
increase
20

–20

–40 –30% Tumor

reduction

–60
PR
PD –80

–100
0 4 8 12 16 0 4 8 12 16
Time (months) Time (months)

B
100

80
Change From Baseline (%)

60

40

20 +20% Tumor increase

–20
–30% Tumor reduction
–40

–60

–80

–100

Fig 2. (A) Treatment exposure and duration of response (n = 24). The length of the bars corresponds with time to the last tumor assessment. (B) Best change from
baseline in tumor size (n = 22). Dotted lines at 20% and 230% indicate the percentage change from baseline and represent progressive disease and partial response,
respectively, per RECIST v1.1. (C) Longitudinal change from baseline in tumor size (n = 24). Dotted lines at 20% and 230% indicate the percentage change from baseline
and represent progressive disease and partial response, respectively, per RECIST v1.1 PD, progressive disease; PR, partial response.

a standard chemotherapeutic combination significantly improved
median OS to 17 months compared with an OS of 13 months with
chemotherapy regimens alone.11 However, increased toxicity was
observed with bevacizumab in this trial, with a higher incidence of
$ grade 3 thromboembolism and $ grade 3 gastrointestinal and
genitourinary fistula, which both remain a significant concern for
patients and physicians.11 These results demonstrate the value of
nonchemotherapeutic agents in that context, and there remains
a need for new alternative agents that are well tolerated and that
improve clinical outcomes.
The PD-1–PD-L1 pathway is known to play a significant role
in oncogenesis, aiding tumor escape from immunosurveillance by
negatively regulating the proliferation and function of tumor-
directed T cells.13,19 Agents that target the PD-1–PD-L1 axis
have been approved for several solid tumor indications, including
melanoma, non–small-cell lung cancer, HNSCC, renal cell carci-
noma, classic Hodgkin lymphoma, and urothelial carcinoma.15,34,35
In recent years, interest in the role of the PD-1–PD-L1 pathway in
the development of virally driven cancers has been growing. In
HNSCC, PD-L1 expression is thought to play a role in the initiation
and persistence of HPV infection by providing an immune-
privileged site where T-cell activity is downregulated.36 PD-L1 is
also highly expressed within HPV-positive HNSCC tumors.36,37
Because virtually all cervical cancers are associated with HPV in-
fection, the role of the PD-1–PD-L1 pathway in HPV-driven tu-
morigenesis is of particular interest within this indication. Although
an association between HPV infection and PD-L1 expression in
cervical tumor cells has previously been identified,19 additional
investigation is required to elucidate the specific contribution of the
PD-1–PD-L1 pathway to HPV-driven cervical tumorigenesis. The

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Copyright © 2019 American Society of Clinical Oncology. All rights reserved.

A B
Progression-Free Survival (%)
100
80
60
40
20
0 5 10
Time (months)
No. at risk
24 6 1
results of the phase I/II study of nivolumab in patients with virus-
associated tumors (CheckMate 358) have been presented for the
recurrent or metastatic cervical, vaginal, and vulvar cancers cohort.38
PD-L1 expression was not mandatory for inclusion and was known
in less than 50% of patients. In a cohort of 19 patients with
cervical cancer, the ORR was 26% (95% CI, 9% to 51%). Of
note, fewer patients in this population had prior treatment: 30%
of patients were receiving front-line treatment for advanced
disease, and only 29% of patients had received two lines or more of
treatment, compared with 63% of patients in our study who received
two or more lines of treatment. Other PD-1–PD-L1 inhibitors, such as
atezolizumab (ClinicalTrials.gov identifier: NCT02921269), durvalu-
mab (ClinicalTrials.gov identifiers: NCT02291055, NCT01975831,
NCT02725489), and nivolumab (ClinicalTrials.gov identifier:
NCT02257528), are currently being investigated for the treatment of
cervical cancer.
In conclusion, results from this analysis of the phase Ib
KEYNOTE-028 trial suggest that pembrolizumab is well tolerated
and has durable antitumor activity in patients with PD-L1–positive
advanced cervical cancer. The safety and clinical benefit of pem-
brolizumab in advanced cervical cancer is currently under in-
vestigation in the open-label, phase II, multicohort KEYNOTE-158
trial (ClinicalTrials.gov identifier: NCT02628067). Additionally, the
predictive value of PD-L1 immunohistochemistry, as well as other
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Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
Frenel et al
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Fig 3. Kaplan-Meier estimates. (A) Progression-
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AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Disclosures provided by the authors are available with this article at
jco.org.
AUTHOR CONTRIBUTIONS
Conception and design: Patrick A. Ott
Provision of study materials or patients: Jean-Sebastien Frenel, Christophe
Le Tourneau, Bert O’Neil, Sarina A. Piha-Paul, Hope S. Rugo
Collection and assembly of data: Jean-Sebastien Frenel, Bert O’Neil,
Patrick A. Ott, Sarina A. Piha-Paul, Carlos Gomez-Roca, Emilie M.J. van
Brummelen, Hope S. Rugo, Shari Thomas, Andrea Varga
Data analysis and interpretation: Jean-Sebastien Frenel, Christophe Le
Tourneau, Bert O’Neil, Patrick A. Ott, Carlos Gomez-Roca, Emilie M.J. van
Brummelen, Sanatan Saraf, Reshma Rangwala
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
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Presented at American Society of Clinical Oncology
Annual Meeting, Chicago, IL, June 2-6, 2017 (abstr
5504)

Affiliations
Jean-Sebastien Frenel, Institut de Cancerologie de l’Ouest, Centre René Gauducheau, Saint-Herblain; Christophe Le Tourneau,
Institut Curie, Paris and Saint-Cloud, and Institut National de la Santé et de la Recherche Médicale U900 Research Unit, Saint-Cloud;
Carlos Gomez-Roca, Institut Claudius Regaud, Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O’Neil, Indiana
University Health University Hospital, Indianapolis, IN; Patrick A. Ott, Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul,
The University of Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The Netherlands Cancer Institute,
Amsterdam, Netherlands; Hope S. Rugo, University of California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf,
and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
Support
Funded by Merck & Co., Inc., Kenilworth, NJ.
Prior Presentation
Presented at the American Society of Clinical Oncology Annual Meeting, Chicago, IL, June 3-7, 2016.

nnn

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 Frenel et al

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1–Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-
028 Trial
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are
self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more
information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Jean-Sebastien Frenel Emilie M.J. van Brummelen
Consulting or Advisory Role: Pfizer, Roche, Eli Lilly, AstraZeneca No relationship to disclose
Travel, Accommodations, Expenses: Roche, Pfizer
Hope S. Rugo
Christophe Le Tourneau Honoraria: Biotheranostics
Honoraria: Merck Sharp & Dohme Research Funding: Plexxikon (Inst), Macrogenics (Inst), OBI Pharma
Consulting or Advisory Role: Merck Sharp & Dohme (Inst), Eisai (Inst), Pfizer (Inst), Novartis (Inst), Eli Lilly (Inst), Genentech
(Inst), Merck (Inst), GTx (Inst)
Bert O’Neil Travel, Accommodations, Expenses: Novartis, Roche/Genentech, Pfizer,
Honoraria: Bayer Puma Biotechnology, Mylan
Consulting or Advisory Role: Amgen, Genentech/Roche, Bayer
Travel, Accommodations, Expenses: Merck KGaA, Bayer Shari Thomas
Employment: Merck
Patrick A. Ott
Consulting or Advisory Role: Amgen, Bristol-Myers Squibb, Alexion Sanatan Saraf
Pharmaceuticals, CytomX Therapeutics, Celldex, Genentech, Neon Employment: Merck
Therapeutics
Research Funding: Bristol-Myers Squibb (Inst), Merck (Inst), Reshma Rangwala
AstraZeneca/MedImmune (Inst), Celldex (Inst), ARMO BioSciences (Inst) Employment: Genmab A/S
Stock or Other Ownership: Merck
Sarina A. Piha-Paul Travel, Accommodations, Expenses: Genmab A/S
Consulting or Advisory Role: Genentech,
Research Funding: GlaxoSmithKline, XuanZhu, Puma Biotechnology, Andrea Varga
Novartis, Merck Sharp & Dohme, Curis, Principia Biopharma, Biomarin, No relationship to disclose
Helix BioPharma, Bayer, Abbvie, Incyte, Five Prime Therapeutics,
Cerulean Pharma, MedImmune, Medivation
Carlos Gomez-Roca
Consulting or Advisory Role: Bristol-Myers Squibb, Novartis,
AstraZeneca
Travel, Accommodations, Expenses: Bristol-Myers Squibb

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 Efficacy of Pembrolizumab in PD-L1–Positive Cervical Cancers

Acknowledgment

We thank the patients, their families, and their caregivers for participating in this trial and all investigators and site personnel. The
authors thank Roger Dansey (Merck) for his critical manuscript review and Anne Morosky and Guoqing Zhao (Merck) for their
contributions to the development of the manuscript. Medical writing and editorial assistance, funded by Merck & Co., Inc., were provided
by Jemimah Walker and Matthew Grzywacz, of the ApotheCom pembrolizumab team (Yardley, PA).

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