Clinical Trial Updates

First-Line Pembrolizumab 1 Chemotherapy Versus

Placebo 1 Chemotherapy for Persistent, Recurrent, or
Metastatic Cervical Cancer: Final Overall Survival Results
of KEYNOTE-826
Bradley J. Monk, MD, FACS, FACOG1 ; Nicoletta Colombo, MD, PhD2,3 ; Krishnansu S. Tewari, MD4 ; Coraline Dubot, MD5;
M. Valeria Caceres, MD, PhD6; Kosei Hasegawa, MD, PhD7 ; Ronnie Shapira-Frommer, MD8; Pamela Salman, MD9 ; Eduardo Yañez, MD10;
Mahmut Gümüş, MD11 ; Mivael Olivera Hurtado de Mendoza, MD12 ; Vanessa Samouëlian, MD, PhD13; Vincent Castonguay, MD14;
Alexander Arkhipov, MD, PhD15; Cumhur Tekin, MD16; Kan Li, PhD16 ; Stephen M. Keefe, MD16; and Domenica Lorusso, MD, PhD17 ; on behalf of
the KEYNOTE-826 Investigators

DOI https://doi.org/10.1200/JCO.23.00914

ABSTRACT ACCOMPANYING CONTENT

Clinical trials frequently include multiple end points that mature at different times. The initial report, Data Supplement
typically based on the primary end point, may be published when key planned co-primary or Protocol
secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate
additional results from studies, published in JCO or elsewhere, for which the primary end point has Accepted September 2, 2023
already been reported. Published November 1, 2023
The phase III, double-blind KEYNOTE-826 trial of pembrolizumab 200 mg or placebo once
every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with or without bev-
acizumab, showed statistically significant survival benefits with the addition of pem-
J Clin Oncol 00:1-7
brolizumab for patients with persistent, recurrent, or metastatic cervical cancer (primary data
© 2023 by American Society of
cutoff: May 3, 2021). This article reports the protocol-specified final overall survival (OS)
Clinical Oncology
results tested in the PD-L1 combined positive score (CPS) ≥1, all-comer, and CPS ≥10 pop-
ulations. At the final data cutoff (October 3, 2022), the median study follow-up duration was
39.1 months (range, 32.1-46.5 months). In the PD-L1 CPS ≥1 (N 5 548), all-comer (N 5 617),
View Online
and CPS ≥10 (N 5 317) populations, median OS with pembrolizumab–chemotherapy versus Article
placebo–chemotherapy was 28.6 months versus 16.5 months (hazard ratio [HR] for death,
0.60 [95% CI, 0.49 to 0.74]), 26.4 months versus 16.8 months (HR, 0.63 [95% CI, 0.52 to
0.77]), and 29.6 months versus 17.4 months (HR, 0.58 [95% CI, 0.44 to 0.78]), respectively.
The incidence of grade ≥3 adverse events was 82.4% with pembrolizumab–chemotherapy and
75.4% with placebo–chemotherapy. These results show that pembrolizumab plus chemo-
therapy, with or without bevacizumab, continued to provide clinically meaningful improve-
ments in OS for patients with persistent, recurrent, or metastatic cervical cancer.

INTRODUCTION ratio [HR], 0.64; P < .001); in the all-comer population,

Pembrolizumab is an anti–PD-1 monoclonal antibody that
has shown promising efficacy and manageable safety as
monotherapy in patients with cervical cancer.1,2 The phase III
KEYNOTE-826 study evaluated the efficacy and safety of
adding pembrolizumab versus placebo to platinum-based
chemotherapy, with or without bevacizumab, as first-line
treatment for persistent, recurrent, or metastatic cervical
cancer.3 Results from the first prespecified interim analysis
showed that the addition of pembrolizumab resulted in
statistically significant and clinically meaningful survival
benefits. In the patients with a PD-L1 combined positive
score (CPS) of 1 or more, median overall survival (OS) was not
reached in the pembrolizumab–chemotherapy group versus
16.3 months in the placebo–chemotherapy group (hazard
median OS was 24.4 months versus 16.5 months, respectively
(HR, 0.67; P < .001).3 Herein, we report the results from the
protocol-specified final OS analysis of KEYNOTE-826.
METHODS
Detailed methods for the KEYNOTE-826 trial (Clinical-
Trials.gov identifier: NCT03635567) were previously pub-
lished.3 Key patient eligibility criteria were age 18 years and
older; persistent, recurrent, or metastatic adenocarcinoma,
adenosquamous carcinoma, or squamous cell carcinoma of
the cervix that was not amenable to curative treatment;
measurable disease per RECIST version 1.1 as assessed by the
investigator; and an Eastern Cooperative Oncology Group
(ECOG) performance status score of 0 or 1. Patients were

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 Monk et al
randomly assigned 1:1 to pembrolizumab 200 mg or placebo
once every 3 weeks for up to 35 cycles. All patients received
chemotherapy (paclitaxel 175 mg/m2 plus either cisplatin
50 mg/m2 or carboplatin AUC 5) once every 3 weeks for six
cycles. Patients could receive bevacizumab 15 mg/kg once
every 3 weeks according to local practice at the investigator’s
discretion. All study medication was administered intrave-
nously. The dual primary end points were OS and
progression-free survival (PFS) assessed per RECIST version
1.1 by investigator review. Secondary end points included the
percentage of patients with confirmed complete or partial
response, duration of response, and the percentage of pa-
tients alive and progression-free at 12 months, all assessed
per RECIST version 1.1 by investigator review, and safety.
Efficacy end points were tested in the PD-L1 CPS ≥1, all-
comer, and CPS ≥10 populations. Tumor imaging was per-
formed at baseline, every 9 weeks through week 54, and
every 12 weeks thereafter. Adverse events (AEs) were graded
according to the National Cancer Institute Common Ter-
minology Criteria for Adverse Events, version 4.0. The study
protocol and all amendments were approved by the inde-
pendent ethics committee or review board at each partici-
pating institution. All patients provided written informed
consent.
RESULTS
Patients
As reported previously,3 the baseline demographics and
disease characteristics were generally well balanced between
the treatment groups (Table 1). All patients, except for one in
the pembrolizumab–chemotherapy group, received at least
one dose of study treatment, and 18 (5.9%) patients in the
pembrolizumab–chemotherapy group and 13 (4.2%) in the
placebo–chemotherapy group remained on study treatment
(Data Supplement, online only). The median follow-up
duration was 39.1 months (range, 32.1-46.5).
Efficacy
At the protocol-specified final analysis (data cutoff: October
3, 2022), pembrolizumab–chemotherapy prolonged OS
compared with placebo–chemotherapy in the PD-L1 CPS ≥1,
all-comer, and CPS ≥10 populations (Figs 1A to 1C). The HRs
for death were <1 in all protocol-specified subgroups, and
the 95% CIs for all subgroups overlapped that of the overall
population (Fig 1D and Data Supplement).
Pembrolizumab–chemotherapy prolonged PFS compared
with placebo–chemotherapy in the PD-L1 CPS ≥1, all-comer,
and CPS ≥10 populations (Table 2 and Data Supplement). In
all populations, the percentage of patients who were alive and
progression-free at 12 months favored the pembrolizumab–
chemotherapy group. The HRs for disease progression or
death were <1 in all protocol-specified subgroups, and the
95% CIs for all subgroups overlapped that of the overall
population (Data Supplement).
2 | © 2023 by American Society of Clinical Oncology
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The percentages of patients with confirmed response per
investigator review were higher in the pembrolizumab–
chemotherapy group than in the placebo–chemotherapy
group in the PD-L1 CPS ≥1, all-comer, and CPS ≥10 pop-
ulations, and there were more complete responses in the
pembrolizumab–chemotherapy group (Table 2). The dura-
tion of response was longer in the pembrolizumab–che-
motherapy group than in the placebo–chemotherapy group
(Table 2 and Data Supplement).
Safety
AEs occurred in 99.3% of patients in the pembrolizumab–
chemotherapy group and 99.4% of patients in the
placebo–chemotherapy group; grade 3-5 AEs occurred in
82.4% and 75.4%, respectively. In both groups, the most
common AEs of any grade were anemia, alopecia, and
nausea, and of grades 3-5 were anemia, neutropenia, and
hypertension (Data Supplement). AEs led to death in 16
patients in the pembrolizumab–chemotherapy group and
15 patients in the placebo–chemotherapy group (5.2% and
4.9%, respectively); of these, two (0.7%) in the
pembrolizumab–chemotherapy and 4 (1.3%) in the
placebo–chemotherapy group were considered related to
treatment (Data Supplement). Potentially immune-
mediated AEs occurred in 34.5% of patients in the
pembrolizumab–chemotherapy group and 16.5% of pa-
tients in the placebo–chemotherapy group, including
12.1% and 2.9%, respectively, who had grade 3-5 AEs (Data
Supplement). Two patients (0.7%) in the pembrolizumab–
chemotherapy group died from immune-mediated AEs
(encephalitis and pancreatitis).
DISCUSSION
At the protocol-specified final analysis of KEYNOTE-826,
first-line treatment with pembrolizumab–chemotherapy,
compared with placebo–chemotherapy, showed enduring
survival benefits for patients with persistent, recurrent, or
metastatic cervical cancer. The addition of pembrolizumab
reduced the risk of death by 40% in the PD-L1 CPS ≥1
population, by 37% in the all-comer population, and by 42%
in the CPS ≥10 population; the risk of disease progression or
death was reduced by 42%, 39%, and 48%, respectively. The
objective response rate remained higher with pembrolizumab–
chemotherapy than with placebo–chemotherapy in each
population, and the responses were durable over longer follow-
up.
The HRs for OS and PFS favored the pembrolizumab–che-
motherapy group in all protocol-specified subgroups.
The Gynecologic Oncology Group 240 trial showed a
survival benefit with bevacizumab, 4 supporting its in-
clusion in the treatment regimen unless contraindicated.
Our findings confirm the activity of pembrolizumab-
chemotherapy regardless of concomitant bevacizumab.
Additionally, a survival benefit with pembrolizumab was
observed in the CPS ≥1 and all-comer populations. In the
 Overall Survival With 1L Pembrolizumab in R/M Cervical Cancer

TABLE 1. Baseline Demographic and Disease Characteristics in the All-Comer Population

Characteristic Pembrolizumab–Chemotherapy (N 5 308) Placebo–Chemotherapy (N 5 309)

Age, years
Median (range) 51 (25-82) 50 (22-79)
≥65, No. (%) 48 (15.6) 52 (16.8)
a
ECOG performance status score, No. (%)
0 178 (57.8) 170 (55.0)
1 128 (41.6) 139 (45.0)
Stage at initial diagnosis, No. (%)b
I 67 (21.8) 58 (18.8)
II 85 (27.6) 93 (30.1)
III 5 (1.6) 8 (2.6)
IIIA 4 (1.3) 8 (2.6)
IIIB 46 (14.9) 42 (13.6)
IVA 7 (2.3) 4 (1.3)
IVB 94 (30.5) 96 (31.1)
Disease status at study entry, No. (%)
Metastaticc 58 (18.8) 64 (20.7)
Persistent or recurrent with distant metastases 199 (64.6) 179 (57.9)
Persistent or recurrent without distant metastases 51 (16.6) 66 (21.4)
Histology, No. (%)d
Adenocarcinoma 56 (18.2) 84 (27.2)
Adenosquamous 15 (4.9) 14 (4.5)
Squamous cell carcinoma 235 (76.3) 211 (68.3)
PD-L1 combined positive score, No. (%)
<1 35 (11.4) 34 (11.0)
≥1 to <10 115 (37.3) 116 (37.5)
≥10 158 (51.3) 159 (51.5)
Previous therapy, No. (%)
Chemoradiation and surgery 49 (15.9) 56 (18.1)
Radiation and surgery 22 (7.1) 23 (7.4)
Chemoradiation only 125 (40.6) 118 (38.2)
Radiation only 31 (10.1) 24 (7.8)
Surgery only 23 (7.5) 24 (7.8)
None 58 (18.8) 64 (20.7)
Bevacizumab use during the study, No. (%)
Yes 196 (63.6) 193 (62.5)
No 112 (36.4) 116 (37.5)

NOTE. From The New England Journal of Medicine, Colombo et al, Pembrolizumab for persistent, recurrent, or metastatic cervical cancer, Volume
No. 385, Page No. 1856-1867 Copyright (C) 2021 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical
Society.3
Abbreviation: ECOG, Eastern Cooperative Oncology Group.
a
ECOG performance status scores range from 0 to 5, with 0 indicating no symptoms and higher scores indicating greater disability. In the
pembrolizumab–chemotherapy group, one (0.3%) patient had ECOG performance status score of 2 and one (0.3%) patient had an unknown score.
b
Determined using International Federation of Gynecology and Obstetrics 2009/National Comprehensive Cancer Network 2017 criteria.
c
Includes patients with para-aortic lymph node involvement. These patients were diagnosed with stage IVB disease and entered the study without
any previous treatment for cervical cancer.
d
In the pembrolizumab–chemotherapy group, histology was recorded as epidermoid carcinoma for one (0.3%) patient and as undifferentiated
carcinoma for one (0.3%) patient.

CPS <1 subgroup, the HR for OS was 0.87; however, the interpretation, these results suggest that the survival
95% CI was wide and overlapped that of the total pop- benefits with pembrolizumab extend across a broad se-
ulation. Although subgroup analyses warrant cautious lection of patients.

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 Monk et al

A OS: PD-L1 CPS t1 Population B OS: All-Comer Population

No. of Events/ Median OS, HR No. of Events/ Median OS, HR
Treatment Group No. of Patients (%) Months (95% CI) (95% CI) Treatment Group No. of Patients (%) Months (95% CI) (95% CI)

Pembro + chemo ± bev 153/273 (56.0) 28.6 Pembro + chemo ± bev 178/308 (57.8) 26.4
(22.1 to 38.0) 0.60 (21.3 to 32.5) 0.63
Placebo + chemo ± bev 201/275 (73.1) 16.5 (0.49 to 0.74) Placebo + chemo ± bev 228/309 (73.8) 16.8 (0.52 to 0.77)
(14.5 to 20.0) (14.6 to 19.4)

100 12-month rate 24-month rate

100 12-month rate 24-month rate
90 75.5% 53.5% 90 74.9% 52.1%
63.2% 39.4% 63.7% 38.7%
80 80
70 70

OS (%)
OS (%)

60 60
50 50
40 40
30 30
20 20
10 10

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48

Time (months) Time (months)

No. at risk: No. at risk:
273 261 251 231 206 189 168 157 146 136 128 116 90 52 22 2 0 308 292 278 256 230 210 187 173 160 150 138 125 95 55 22 2 0
275 261 235 207 173 149 129 117 107 91 81 68 45 24 3 0 0 309 295 268 235 196 170 149 130 118 101 87 72 48 26 3 0 0

C OS: PD-L1 CPS t10 Population D OS: Protocol-Specified Subgroups, All-Comer Population
No. of Events/ Median OS, HR No. of Events/
Treatment Group No. of Patients (%) Months (95% CI) (95% CI) Subgroup No. of Patients HR (95% CI)

Pembro + chemo ± bev 85/158 (53.8) 29.6 Overall 406/617 0.63 (0.52-0.77)
(20.6 to NR) 0.58 Age, years
Placebo + chemo ± bev 114/159 (71.7) 17.4 (0.44 to 0.78)
<65 345/517 0.60 (0.49-0.75)
(14.0 to 24.7)
t65 61/100 0.84 (0.48-1.46)
100 Race
12-month rate 24-month rate
90 75.9% 54.4% White 238/360 0.63 (0.49-0.83)
61.6% 42.5% All others 144/221 0.62 (0.44-0.87)
80
70 ECOG performance status score
0 192/348 0.62 (0.46-0.83)
OS (%)

60
50 1 212/267 0.68 (0.51-0.91)
40 PD-L1 combined positive score
30 <1 52/69 0.87 (0.50-1.52)
20 1 to <10 155/231 0.63 (0.45-0.86)
10 t10 199/317 0.58 (0.44-0.78)
Concomitant bevacizumab
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Yes 229/389 0.61 (0.47-0.80)
No 177/228 0.67 (0.49-0.91)
Time (months)
Metastatic disease at diagnosis
No. at risk:
Yes 135/190 0.85 (0.60-1.21)
158 150 145 134 120 112 98 91 86 80 76 67 51 31 15 1 0
159 151 135 116 97 87 76 70 66 53 48 39 23 10 0 0 0 No 271/427 0.54 (0.43-0.70)

0.25 0.5 1.0 2.0 4.0

Favors Favors
Pembro + Placebo +
Chemo ± Bev Chemo ± Bev

FIG 1. Kaplan-Meier estimates of OS (A) in the PD-L1 CPS ≥1 population, (B) in the all-comer population, and (C) in the PD-L1 CPS ≥10 population,
and (D) an analysis of OS in protocol-specified subgroups of the all-comer population. The stratified Cox models were used to estimate the hazard ratios
shown in A, B, and C, with the proportional hazards assumption assessed via examining the scaled Schoenfeld residuals, and the results suggested the
proportional hazards assumption was not violated in these models. Tick marks in A, B, and C indicate censoring of data. bev, bevacizumab; chemo,
chemotherapy; CPS, combined positive score; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; OS, overall survival.

The safety profile of pembrolizumab–chemotherapy after was no evidence of cumulative toxicity over time, and the
longer follow-up remained similar to that reported in the addition of pembrolizumab did not increase the rates of
previous interim analysis,3 and is consistent with the known known toxicities associated with chemotherapy and bev-
profiles of the individual treatment components.1,2,4-6 There acizumab. As anticipated, the incidence of potentially

4 | © 2023 by American Society of Clinical Oncology

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 Journal of Clinical Oncology

TABLE 2. Summary of Efficacy End Points Assessed per RECIST Version 1.1 by Investigator Review

PD-L1 CPS ≥1 All-Comer PD-L1 CPS ≥10

Pembrolizumab– Placebo–Chemotherapy Pembrolizumab– Placebo–Chemotherapy Pembrolizumab– Placebo–Chemotherapy

End Point Chemotherapy (N 5 273) (N 5 275) Chemotherapy (N 5 308) (N 5 309) Chemotherapy (N 5 158) (N 5 159)
Median PFS, months (95% CI) 10.5 (9.7 to 12.3) 8.2 (6.3 to 8.5) 10.4 (9.1 to 12.2) 8.2 (6.4 to 8.4) 10.4 (8.9 to 15.1) 8.1 (6.2 to 8.8)

Overall Survival With 1L Pembrolizumab in R/M Cervical Cancer

12-month PFS rate, % 45.6 33.7 44.7 33.1 44.7 33.5
HR for PFS (95% CI) 0.58 (0.47 to 0.71) 0.61 (0.50 to 0.74) 0.52 (0.40 to 0.68)
Objective response, % (95% CI) 68.5 (62.6 to 74.0) 50.9 (44.8 to 57.0) 66.2 (60.7 to 71.5) 51.5 (45.7 to 57.2) 69.6 (61.8 to 76.7) 50.3 (42.3 to 58.3)
Complete response, No. (%) 70 (25.6) 40 (14.5) 76 (24.7) 44 (14.2) 39 (24.7) 20 (12.6)
Partial response, No. (%) 117 (42.9) 100 (36.4) 128 (41.6) 115 (37.2) 71 (44.9) 60 (37.7)
Stable disease, No. (%) 57 (20.9) 86 (31.3) 68 (22.1) 97 (31.4) 29 (18.4) 51 (32.1)
Progressive disease, No. (%) 9 (3.3) 29 (10.5) 15 (4.9) 33 (10.7) 4 (2.5) 16 (10.1)
Not evaluable, No. (%)a 1 (0.4) 2 (0.7) 1 (0.3) 2 (0.6) 1 (0.6) 2 (1.3)
b
Not assessed, No. (%) 19 (7.0) 18 (6.5) 20 (6.5) 18 (5.8) 14 (8.9) 10 (6.3)
Patients with response, No. (%) 187 (68.5) 140 (50.9) 204 (66.2) 159 (51.5) 110 (69.6) 80 (50.3)
Response duration, months, 19.2 (1.31-40.91) 10.4 (1.51-40.71) 18.0 (1.31-40.91) 10.4 (1.51-40.71) 28.3 (1.31-40.91) 10.1 (2.11-38.31)
median (range)
Extended response duration,
months, No. (%)
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≥12 98 (55.9) 57 (45.3) 106 (55.1) 64 (45.9) 60 (58.6) 32 (44.1)

≥24 81 (47.8) 36 (29.8) 88 (47.3) 37 (27.6) 50 (50.8) 20 (28.6)
Time to response, months, 2.1 (1.7-23.5) 2.1 (1.3-20.6) 2.1 (1.7-23.5) 2.1 (1.3-20.6) 2.2 (1.7-8.4) 2.1 (1.3-20.6)
median (range)

Abbreviations: CPS, combined positive score; HR, hazard ratio; PFS, progression-free survival.
a
Patients who had ≥1 postbaseline imaging assessment, none of which could be evaluated for response according to RECIST version 1.1.
b
Patients who did not have any postbaseline imaging assessment.

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 Monk et al

immune-mediated AEs was higher in the pembrolizumab
group; however, chemotherapy and bevacizumab did not
exacerbate these events.
In conclusion, the protocol-specified final analysis results of
KEYNOTE-826 continue to show that pembrolizumab plus
platinum-based chemotherapy provides substantial and
clinically meaningful survival improvements compared with
platinum-based chemotherapy in patients with persistent,
recurrent, or metastatic cervical cancer. These findings
confirm the previous interim data,3 and provide further
support for first-line pembrolizumab plus chemotherapy,
with or without bevacizumab, as a standard of care for
persistent, recurrent, or metastatic cervical cancer.

AFFILIATIONS AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS

1
HonorHealth Research Institute, University of Arizona College of
OF INTEREST
Medicine, Creighton University School of Medicine, Phoenix, AZ Disclosures provided by the authors are available with this article at DOI
2
Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, https://doi.org/10.1200/JCO.23.00914.
Italy
3
Università degli Studi di Milano Bicocca, Milan, Italy DATA SHARING STATEMENT
4
Obstetrics & Gynecology, University of California, Irvine, Orange, CA
5 Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Rahway, NJ
Oncologie Médicale, Institut Curie Saint Cloud, and GINECO, Paris,
(MSD), is committed to providing qualified scientific researchers access
France
6 to anonymized data and clinical study reports from the company’s
Medical Oncology, Instituto de Oncologia Angel H. Roffo, Buenos Aires,
clinical trials for the purpose of conducting legitimate scientific
Argentina
7 research. MSD is also obligated to protect the rights and privacy of trial
Gynecologic Oncology, Saitama Medical University International
participants and, as such, has a procedure in place for evaluating and
Medical Center, Hidaka, Japan
8 fulfilling requests for sharing company clinical trial data with qualified
Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center,
external scientific researchers. The MSD data sharing website
Ramat Gan, Israel
9 (available at: http://engagezone.msd.com/ds_documentation.php)
Medical Oncology, Oncovida Cancer Center, Providencia, Santiago,
outlines the process and requirements for submitting a data request.
Chile
10 Feasible requests will be reviewed by a committee of MSD subject
Medical Oncology, Universidad de la Frontera, Temuco, Chile
11 matter experts to assess the scientific validity of the request and the
Medical Oncology, Istanbul Medeniyet University Hospital, Istanbul,
qualifications of the requestors. In line with data privacy legislation,
Turkey
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Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas,
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Lima, Peru
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Gynecologic Oncology, Centre Hospitalier de l’Université de Montréal
and European Union or after product development is discontinued.
(CHUM), Centre de Recherche de l’Université de Montréal (CRCHUM),
There are circumstances that may prevent MSD from sharing requested
Université de Montréal, Montreal, QC, Canada
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Université Laval, Quebec City, QC, Canada
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matter experts; after approval of the statistical analysis plan and
Federation
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Gynaecology Oncology Unit, Fondazione Policlinico Universitario A
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Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy
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CORRESPONDING AUTHOR
Bradley J. Monk, MD, FACS, FACOG, University of Arizona College of AUTHOR CONTRIBUTIONS
Medicine, Creighton University School of Medicine, 3100 N Central Ave,
Conception and design: Bradley J. Monk, Krishnansu S. Tewari, Kosei
Phoenix, AZ 85012; e-mail: bmonk@gog.org.
Hasegawa, Pamela Salman, Cumhur Tekin, Kan Li, Stephen M. Keefe
Administrative support: Stephen M. Keefe
PRIOR PRESENTATION Provision of study materials or patients: Krishnansu S. Tewari, Coraline
Presented at the ASCO 2023 Annual Meeting, Chicago, IL, June 2-6, Dubot, M. Valeria Caceres, Ronnie Shapira-Frommer, Pamela Salman,
2023. Eduardo Yañez, Mivael Olivera Hurtado de Mendoza
Collection and assembly of data: Bradley J. Monk, Krishnansu S. Tewari,
SUPPORT Kosei Hasegawa, Pamela Salman, Eduardo Yañez, Mivael Olivera
Hurtado de Mendoza, Vanessa Samouëlian, Alexander Arkhipov,
Supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co,
Cumhur Tekin, Kan Li, Stephen M. Keefe, Domenica Lorusso on behalf of
Inc, Rahway, NJ.
the KEYNOTE-826 investigators
Data analysis and interpretation: Bradley J. Monk, Nicoletta Colombo,
CLINICAL TRIAL INFORMATION Krishnansu S. Tewari, Coraline Dubot, M. Valeria Caceres, Kosei
NCT03635567 Hasegawa, Ronnie Shapira-Frommer, Pamela Salman, Eduardo Yañez,

6 | © 2023 by American Society of Clinical Oncology

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 Overall Survival With 1L Pembrolizumab in R/M Cervical Cancer

Vanessa Samouëlian, Vincent Castonguay, Alexander Arkhipov, Kan Li, following employees of Merck Sharp & Dohme LLC, a subsidiary of
Stephen M. Keefe Merck & Co, Inc, Rahway, NJ: Gursel Aktan for input into the trial design;
Manuscript writing: All authors Sarper Toker for study oversight; Amy Blum, Aline Galvao, and Soodaba
Final approval of manuscript: All authors Mir for study support; Ying Zhang and Jing Zhao for statistical support;
Accountable for all aspects of the work: All authors Christine McCrary Sisk for medical writing support; and Michele
McColgan for editorial assistance.
ACKNOWLEDGMENT A complete list of investigators who participated in the KEYNOTE-826
study is provided in the Data Supplement.
The authors thank the patients and their families and caregivers for
participating in the study; the investigators and site personnel; and the

REFERENCES
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2. Chung HC, Ros W, Delord JP, et al: Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 37:1470-1478,
2019
3. Colombo N, Dubot C, Lorusso D, et al: Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 385:1856-1867, 2021
4. Tewari KS, Sill MW, Penson RT, et al: Bevacizumab for advanced cervical cancer: Final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic
Oncology Group 240). Lancet 390:1654-1663, 2017
5. Monk BJ, Sill MW, McMeekin DS, et al: Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: A Gynecologic Oncology Group study.
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 Monk et al

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

First-Line Pembrolizumab 1 Chemotherapy Versus Placebo 1 Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall
Survival Results of KEYNOTE-826

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless
otherwise noted. Relationships are self-held unless noted. I 5 Immediate Family Member, Inst 5 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/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open
Payments).

Bradley J. Monk Kosei Hasegawa

Leadership: US Oncology
Honoraria: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca,
Clovis Oncology, Eisai, Genmab/Seattle Genetics, ImmunoGen, Iovance
Biotherapeutics, Merck, Mersana, Pfizer, Puma Biotechnology,
Regeneron, Roche/Genentech, TESARO/GSK, Vascular Biogenics, GOG
Foundation, Elevar Therapeutics, Novocure, Gradalis, Karyopharm
Therapeutics, Bayer, EMD Serono/Merck, Sorrento Therapeutics, US
Oncology, Myriad Pharmaceuticals, Novartis, OncoC4, Pieris
Pharmaceuticals, Acrivon Therapeutics, Adaptimmune, HenRui, Laekna
Health Care, Panavance Therapeutics, Verastem, Zentalis
Consulting or Advisory Role: Agenus, Akeso Biopharma, Amgen,
Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics,
GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck,
Mersana, Myriad Pharmaceuticals, Pfizer, Puma Biotechnology,
Regeneron, Roche/Genentech, TESARO/GSK, Vascular Biogenics,
Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, Novocure,
Bayer, Elevar Therapeutics, EMD Serono/Merck, Gradalis, US Oncology,
Novartis, Pieris Pharmaceuticals, OncoC4, Adaptimmune, HenRui,
Laekna Health Care, Panavance Therapeutics, Verastem, Zentalis
Speakers’ Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology,
Eisai, TESARO/GSK, Merck
Research Funding: Novartis (Inst), Amgen (Inst), Genentech (Inst), Lilly
(Inst), Janssen (Inst), Array BioPharma (Inst), Tesaro (Inst), Morphotek
(Inst), Pfizer (Inst), Advaxis (Inst), AstraZeneca (Inst), Immunogen (Inst),
Regeneron (Inst), Nucana (Inst)
Honoraria: MSD K.K, Daiichi Sankyo, Chugai Pharma, AstraZeneca,
Eisai, Kyowa Kirin, Takeda, Sanofi, Genmab
Consulting or Advisory Role: MSD K.K, Kaken Pharmaceutical, Daiichi
Sankyo, Roche, Genmab, Takeda, Sanofi
Research Funding: Ono Pharmaceutical, Daiichi Sankyo, Merck
Ronnie Shapira-Frommer
Honoraria: MSD Oncology, Bristol Myers Squibb, Novartis, Roche,
AstraZeneca, medison, Neopharm, MSD, AstraZeneca, MSD (Inst)
Consulting or Advisory Role: Vascular Biogenics, Clovis Oncology, MSD
Oncology
Pamela Salman
Consulting or Advisory Role: Roche/Genentech, Novartis, Lilly, Merck
Serono
Speakers’ Bureau: Roche/Genentech, Novartis, Lilly
Eduardo Yañez
Honoraria: Abbott Laboratories
Consulting or Advisory Role: Merck Serono, Abbott Laboratories, Bristol
Myers Squibb
Research Funding: AbbVie (Inst), Pfizer (Inst), Bristol Myers Squibb
(Inst), Exelis (Inst), MSD, Roche, Amgen
Expert Testimony: Abbott Laboratories
Travel, Accommodations, Expenses: Bristol Myers Squibb, Amgen

Nicoletta Colombo Mahmut Gümüş

Employment: Sarepta Therapeutics
Honoraria: Roche/Genentech, AstraZeneca, GlaxoSmithKline, MSD
Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Pfizer,
mersana, Eisai, Advaxis, Nuvation Bio
Consulting or Advisory Role: Roche/Genentech, AstraZeneca, Clovis
Oncology, Pfizer, MSD Oncology, GlaxoSmithKline, Immunogen, Pfizer,
mersana, Eisai, Advaxis, Nuvation Bio
Krishnansu S. Tewari
Honoraria: Tesaro, Clovis Oncology, Merck, Eisai, AstraZeneca, Genmab
Consulting or Advisory Role: Roche/Genentech, Tesaro, Clovis
Oncology, AstraZeneca
Speakers’ Bureau: Roche/Genentech, AstraZeneca, Merck, Tesaro,
Clovis Oncology, Eisai, Genmab
Research Funding: AbbVie (Inst), Genentech/Roche (Inst), Morphotek
(Inst), Merck (Inst), Regeneron (Inst)
Travel, Accommodations, Expenses: Roche/Genentech
Honoraria: MSD Oncology (Inst), Pfizer (Inst), GlaxoSmithKline (Inst),
Novartis (Inst)
Consulting or Advisory Role: Roche, Lilly (Inst), Amgen (Inst), Gen (Inst),
Novartis (Inst), Takeda (Inst), Gilead Sciences (Inst)
Speakers’ Bureau: Roche (Inst), MSD Oncology (Inst), Novartis (Inst),
Polipharma (Inst), Amgen (Inst)
Research Funding: Amgen (Inst), Pfizer (Inst), Takeda (Inst)
Travel, Accommodations, Expenses: Pfizer
Vanessa Samouëlian
Honoraria: GlaxoSmithKline, Merck
Consulting or Advisory Role: Merck
Vincent Castonguay
Consulting or Advisory Role: AstraZeneca, BMS, Janssen, Ipsen, Eisai,
Pfizer, Astellas Pharma, Merck, GlaxoSmithKline Canada, Bayer
Research Funding: Merck (Inst), Pfizer (Inst), AstraZeneca Canada
(Inst), Bayer (Inst), Bristol Myers Squibb/Celgene (Inst)

Cumhur Tekin
Employment: Merck, Novo Nordisk
Stock and Other Ownership Interests: Merck

© 2023 by American Society of Clinical Oncology

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 Overall Survival With 1L Pembrolizumab in R/M Cervical Cancer

Kan Li Domenica Lorusso

Employment: Merck
Stock and Other Ownership Interests: Merck
Stephen M. Keefe
Employment: Merck Sharp & Dohme
Stock and Other Ownership Interests: Merck Sharp & Dohme
Travel, Accommodations, Expenses: Merck Sharp & Dohme
Consulting or Advisory Role: PharmaMar, AstraZeneca, Clovis
Oncology, GlaxoSmithKline, MSD, Genmab, Seagen, Immunogen,
Oncoinvest, Corcept Therapeutics, Sutro Biopharma, Novartis
Speakers’ Bureau: AstraZeneca, Clovis Oncology, GlaxoSmithKline,
MSD, PharmaMar, ImmunoGen, Seagen, Genmab
Research Funding: PharmaMar (Inst), Clovis Oncology (Inst),
GlaxoSmithKline (Inst), MSD (Inst), AstraZeneca (Inst), Clovis Oncology
(Inst), GlaxoSmithKline (Inst), MSD (Inst), Genmab (Inst), Seagen (Inst),
Immunogen (Inst), Incyte (Inst), Novartis (Inst), Roche (Inst)
Travel, Accommodations, Expenses: AstraZeneca, Clovis Oncology,
GlaxoSmithKline
Uncompensated Relationships: Gynecological Cancer InterGroup
No other potential conflicts of interest were reported.

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