Update on clinical trials in cervical cancer

Updates on Clinical Trials in Cervical Cancer
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín, Colombia
Hotel Intercontinental,
Medellín, 23.06.2017

Trials in the non-metastatic
setting
Trials in the metastatic
setting
Topics

Trials in the non-metastatic setting
The advent of chemo-radiation therapy
 Prior to 1999 locally advanced (non-
surgical/non-metastatic) cervical cancer
was treated with radiation therapy and
intracavitary therapy
 Long-term overall survival (OS) in stage III
was about 40-50%
 That all changed on April 15, 1999…

Stage IB2 (>4 cm) Cervical
Cancer
N0 by CT/FNA/Surgery
PS 0-3
Suitable for hysterectomy
Adequate organ function
External Radiotherapy with
Concurrent weekly
Cisplatin (40 mg/m2, max 70 mg,
x6)
Intracavitary brachytherapy
Extrafascial hysterectomy*
Extrafascial hysterectomy*
Endpoints
PFS
OS
75 Gy to point A, 55 Gy to point B
*Extrafascial hysterectomy post
irradiation was deemed
necessary in 1992 when this
study was initiated. That is no
longer the case
GOG-123
Weekly Cisplatin Chemotherapy during Irradiation
Improves Survival and Reduces Relapses for
patients with Bulky Stage IB Cervical Cancer
Treated with Irradiation and Adjuvant Hysterectomy
Keys, H. M., Bundy, B. N., Stehman, F. B., Muderspach, L. I., Chafe, W. E., Suggs, C. L., … Gersell, D. (1999). Cisplatin, Radiation, and Adjuvant
Hysterectomy Compared with Radiation and Adjuvant Hysterectomy for Bulky Stage IB Cervical Carcinoma. New England Journal of Medicine,
340(15), 1154–1161. https://doi.org/10.1056/NEJM199904153401503

Stage IB:
Confined to the cervix
Depth more than 5 mm
Width more than 7 mm

Bulky Stage IB:
Confined to the cervix
More than 4 cm

GOG-123
Weekly Cisplatin Chemotherapy during Irradiation Improves Survival and Reduces Relapses for patients with
Bulky Stage IB Cervical Cancer Treated with Irradiation and Adjuvant Hysterectomy
PFS (%)
OS (%) - Median F/U of 36 mo
Underwent hysterectomy (%)
Concurrent chemo-RT
RT
35* 79*
85*
74*
63*15*
Grade ¾ toxicity
* Statistically significant
96%
90
n=369

GOG-123
PFS (%)
Underwent hysterectomy (%)
Concurrent chemo-RT
RT
35* 79*
85*
74*
63*15*
Grade ¾ toxicity
96
90
n=369

GOG-123

Stage IIB-IVA Cervical
cancer
N0 by CT and
lymphadenectomy
PS 0-3
External Radiotherapy with Concurrent
weekly
Cisplatin (40 mg/m2, max 70 mg, x6)
Concurrent hydroxyurea
Endpoints
OS
PFS
RT dosages
Stage II: 80.8 Gy to point A, 55 Gy to point B
Stage III-IVA: 81 Gy to point A, 60 Gy to point B
GOG-120
Concurrent Cisplatin-Based
Radiotherapy and Chemotherapy for
Locally Advanced Cervical Cancer
Rose, P. G., Bundy, B. N., Watkins, E. B., Thigpen, J. T., Deppe, G., Maiman, M. A., … Insalaco, S. (1999). Concurrent Cisplatin-
Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer. New England Journal of Medicine, 340(15),
1144–1153. https://doi.org/10.1056/NEJM199904153401502
Concurrent Cisplatin / FU /
Hydroxyurea

Rose, P. G., Bundy, B. N., Watkins, E. B., Thigpen, J. T., Deppe, G., Maiman, M. A., … Insalaco, S. (1999). Concurrent Cisplatin-Based
Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer. New England Journal of Medicine, 340(15), 1144–1153.
https://doi.org/10.1056/NEJM199904153401502
GOG-120: Concurrent Cisplatin-Based Radiotherapy and Chemotherapy
for Locally Advanced Cervical Cancer

Rose, P. G., Bundy, B. N., Watkins, E. B., Thigpen, J. T., Deppe, G., Maiman, M. A., … Insalaco, S. (1999). Concurrent Cisplatin-Based
Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer. New England Journal of Medicine, 340(15), 1144–1153.
https://doi.org/10.1056/NEJM199904153401502
GOG 120: Concurrent Cisplatin-Based Radiotherapy and Chemotherapy
for Locally Advanced Cervical Cancer
PFS at 24 mo(%)
Concurrent Cisplatin-RT
Concurrent hydroxyurea-RT
46*
67*
66*
49*
64*21*
Grade ¾ Leucopenia
Concurrent Cisplatin/FU/Hydroxyurea-RT
47*
67*
23*
n=526

Stage IIB-IVA
or Stage IB or IIA (>5 cm)
or Biopsy-proven pelvic
metastasis
Cervical cancer
KPS >60%
External Radiotherapy with Concurrent
weekly
Cisplatin + Fluoruracil infusion q3w
Concurrent hydroxyurea
Endpoints
OS
PFS
RTOG
Pelvic Radiation with Concurrent Chemotherapy
Compared with Pelvic and Para-Aortic Radiation for
High-Risk Cervical Cancer
Morris, M., Eifel, P. J., Lu, J., Grigsby, P. W., Levenback, C., Stevens, R. E., … Mutch, D. G. (1999). Pelvic Radiation with
Concurrent Chemotherapy Compared with Pelvic and Para-Aortic Radiation for High-Risk Cervical Cancer. New England
Journal of Medicine, 340(15), 1137–1143. https://doi.org/10.1056/NEJM199904153401501

Morris, M., Eifel, P. J., Lu, J., Grigsby, P. W., Levenback, C., Stevens, R. E., … Mutch, D. G. (1999). Pelvic Radiation with Concurrent
Chemotherapy Compared with Pelvic and Para-Aortic Radiation for High-Risk Cervical Cancer. New England Journal of Medicine,
RTOG
Pelvic Radiation with Concurrent Chemotherapy Compared with Pelvic and Para-Aortic Radiation
for High-Risk Cervical Cancer
PFS at 24 mo(%)
RT
67*
73*
58*
65*
Locoregional disease control (%)
Concurrent Cisplatin/FU-RT
40*79*
86*
Distant-metastasis free (%)
67*
n=403

Improved Treatment for Cervical Cancer —
Concurrent Chemotherapy and Radiotherapy
Thomas, G. M. (1999). Improved Treatment for Cervical Cancer ? Concurrent Chemotherapy and Radiotherapy. New
England Journal of Medicine, 340(15), 1198–1200. https://doi.org/10.1056/NEJM199904153401509

Reducing uncertainties about the effects of chemoradiotherapy for cervical
cancer: a systematic review and meta-analysis of individual patient data from 18
randomized trials.
Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Cli

Stage Absolute 5-yr survival benefit
Ib-IIa 10%
IIb 7%
III-IVa 3%
Reducing uncertainties about the effects of chemoradiotherapy for
cervical cancer: a systematic review and meta-analysis of individual
patient data from 18 randomized trials.
Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Cli

New “standard-of-care” in
stage IB2-IVA is concurrent
Cisplatin and RT

Stage IIB-IVA
squamous
cervical cancer
KPS >60%
Neoadjuvant CT (Cisplatin +
Vincristine + Bleomycin) x3
followed by RT and intracavitary
RT
Concurrent Cisplatin and
intracavitary RT
Endpoints
6-mo and 12-mo DCR (disease-control rate)
Is neo-adjuvant chemotherapy a
better option for management of
cervical cancer patients of rural India?
Dastidar, G. A., Gupta, P., Basu, B., Basu, A., Shah, J. K., & Seal, S. L. (2016). Is neo-adjuvant chemotherapy a better option for management of cervical cancer patients of rural India? Indian Journal of
Cancer, 53(1), 56–9. https://doi.org/10.4103/0019-509X.180826
Rural-based
Urban-based
n=200
n=390

Stage IB2
cervical cancer
PS 0-2
NACT (Vincristine + Cisplatin)
followed by RHPPL
Radical histerectomy and
pelvic/para-aortic lymph-node
dissection (RHPPL)
Endpoints
PFS and OS
GOG-141: Treatment of ("bulky") stage IB cervical cancer with or without neoadjuvant vincristine
and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: a phase III
trial of the gynecologic oncology group.
Eddy, G. L., Bundy, B. N., Creasman, W. T., Spirtos, N. M., Mannel, R. S., Hannigan, E., & O?Connor, D. (2007). Treatment of (?bulky?) stage IB cervical cancer with or without neoadjuvant vincristine
and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: A phase III trial of the gynecologic oncology group. Gynecologic Oncology, 106(2), 362–369.
https://doi.org/10.1016/j.ygyno.2007.04.007
n=291
Closed due to low accrual

Stage IB2, IIA2, IIB
squamous cervical cancer
By MRI
20-70
PS 0 or 1
Neoadjuvant CT (BOMP: Cisplatin
+ Vincristine + Mitomycin +
Bleomycin) x3, followed by Radical
Surgery (NACT-RS)
Radical surgery (RS)
Endpoint
OS
Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery
vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical
Oncology Group trial (JCOG 0102)
Katsumata, N., Yoshikawa, H., Kobayashi, H., Saito, T., Kuzuya, K., Nakanishi, T., … Japan Clinical Oncology Group. (2013). Phase III randomised controlled trial of neoadjuvant chemotherapy plus
radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102). British Journal of Cancer, 108(10), 1957–63.
https://doi.org/10.1038/bjc.2013.179
n=134
Post surgical RT if high risk pathology after RS
Pelvic lymph node metastasis,
parametrial involvement,
or deep stromal invasion (⩾2/3).

Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery
vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical
Oncology Group trial (JCOG 0102)
Katsumata, N., Yoshikawa, H., Kobayashi, H., Saito, T., Kuzuya, K., Nakanishi, T., … Japan Clinical Oncology Group. (2013). Phase III randomised controlled trial of neoadjuvant chemotherapy plus
radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102). British Journal of Cancer, 108(10), 1957–63.
https://doi.org/10.1038/bjc.2013.179

Stage IIB to IVA
cervical cancer
KPS ≥ 70%
Cisplatin + Gemcitabine (40 + 125 mg/m2,
q1w) + concurrent RT, followed by
intracavitary RT, followed by
Adjuvant CT with Cisplatin +
Gemcitabine (50 mg/m2 d1, 1000 mg/m2 d1 &
d8, q21d) x2 cycles
Cisplatin (40 mg/m2, q1w) + concurrent
RT, followed by intracavitary RT
Endpoint
PFS @ 3-yr
Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin
and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin
and radiation in patients with stage IIB to IVA carcinoma of the cervix.
Dueñas-González, A., Zarb?, J. J., Patel, F., Alcedo, J. C., Beslija, S., Casanova, L., … Orlando, M. (2011). Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and
Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix. Journal of Clinical Oncology, 29(13),
1678–1685. https://doi.org/10.1200/JCO.2009.25.9663
n=515
Weekly Cis
RT (external / intracavitary)
Standard of care (control)
Weekly Cis + Gem
Experimental arm
Adjuvant Cis + Gem

FIGO Stages IIB-IVA Cervical cancer (Locally-advanced Cervical Cancer – LACC)
PFS a 3 años:
74%
OS a 3 años:
78.2%
PFS a 3 años:
65%
OS a 3 años:
69.1%
CisRT
Gemcitabina
CisRT
 Gemcitabine + CisRT: Gemcitabine
125 mg/m2 qW x6 + Cisplatio 40
mg/m2 qWx6 (concurrent with RT).
Then intracavitary RT, followed by 2
cycles of adjuvant CT with Cisplatin+
Gemcitabine.
 CisRT: Cisplatin 40 mg/m2 qW x6
(concurrent with RT). Followed by
intracavitary RT
 HR para PFS: 0.68,
p=0.02
 HR para OS: 0.68,
p=0.022
LACC
GenCisRT en LACC
n=515
n=259 n=256
LemaTeachFiles® - 2009Dueñas-González, A. et al. J Clin Oncol 27:18s, 2009 (suppl; abstr CRA5507)

LemaTeachFiles® - 2009Dueñas-González, A. et al. J Clin Oncol 27:18s, 2009 (suppl; abstr CRA5507)
FIGO Stages IIB-IVA Cervical cancer (Locally-advanced Cervical Cancer – LACC)

1678–1685. https://doi.org/10.1200/JCO.2009.25.9663
PFS at 3-yr mo(%)
OS at 3-yr (%)
74*
78*
46*
Grade 3/4 toxicities (%)
Cisplatin + Gemcitabine + RT (external and intracavitary),
adjuvant Cisplatin + Gemcitabine
65*86*
2
Treatment-related deaths (n)
n=515
Cisplatin + RT (external and intracavitary),
69*

1678–1685. https://doi.org/10.1200/JCO.2009.25.9663
PFS at 3-yr mo(%)
OS at 3-yr (HR with 95% C.I.)
74*
0.68 (0.49-0.95)
46*
Grade 3/4 toxicities (%)
Cisplatin + Gemcitabine + RT (external and intracavitary),
adjuvant Cisplatin + Gemcitabine
65*86*
2
Treatment-related deaths (n)
n=515
Cisplatin + RT (external and intracavitary),

Stage IB1 & node positive, IB2, IIA,
IIB, IIIB, or IVA disease
cervical cancer
PS 0-2
Adequate organ function Cisplatin (40 mg/m2, q1w) + concurrent
RT, followed by intracavitary RT
Endpoint
OS
OUTBACK: Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel
in Patients With Locally Advanced Cervical Cancer
clinicaltrials.gov - NCT01414608 (Moore K, NRG)
Ongoing
Weekly Cis
Standard of care (control)
Experimental arm
Adjuvant Pacl + Carbo
Cisplatin (40 mg/m2, q1w) + concurrent
RT, followed by intracavitary RT,
followed by Pacl + Carbo q3w
x4
Weekly Cis

Neoadjuvant or Adjuvant
chemotherapy are NOT current
standards-of-care, but the issue is
far from settled.

Trials in the metastatic, persistent/recurrent disease
Systemic therapy is often the only option
 Cisplatin, introduced in the 80’s offered
modest short-term control in advanced
cervical cancer…

Early trials in metastatic cervical cancer
Trials
• GOG43 (1987)
• GOG64 (1989)
• GOG77 (1989)
• GOG110 (1997)
• GOG 149 (2002)
Research (C = Cisplatin)
Coleman RL. The Gynecologic Oncology Group's role in the treatment of recurrent
cervix cancer: Current clinical trials. Gynecologic Oncology, Volume 110, Issue 3,
Supplement 2, September 2008, Pages S77-S80
• C: 50 mg/m2 vs 100 mg/m2
• C: Short vs long infusion
• C vs C+Ifosfamide (C/Ifo)
• C/Ifo vs C/Ifo/Bleomycin

Early trials in metastatic cervical cancer
Trials
• GOG43 (1987)
• GOG64 (1989)
• GOG77 (1989)
• GOG110 (1997)
• GOG 149 (2002)
Summary results
• Low-dose Cisplatin (50 mg/m2)
• ORR: 21%
• Median OS: 7.1 mo
• Carboplatin o irinotecán
• ORR: 15%
• Median OS: 6.2 mo
• High-dose Cisplatin improves ORR but not OS
• Cisplatin plus Ifosfamide and Bleomycin
• ORR: 31%
• OS: 8.5 mo
Coleman RL. The Gynecologic Oncology Group's role in the treatment of recurrent
cervix cancer: Current clinical trials. Gynecologic Oncology, Volume 110, Issue 3,
Supplement 2, September 2008, Pages S77-S80

Stage IVB, recurrent, or persistent
disease that was not amenable to
curative treatment with surgery or
radiation therapy
PS 0-2
Paclitaxel at an IV dose of 135
mg/m2 as a 24-hour infusion
followed immediately by cisplatin at a
dose of 50 mg/m2
cisplatin IV dose of 50 mg/m2
Endpoints
Response-rate, PFS or OS
GOG-169: Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent,
or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group
study.
Moore, D. H., Blessing, J. A., McQuellon, R. P., Thaler, H. T., Cella, D., Benda, J., … Rocereto, T. F. (2004). Phase III Study of Cisplatin With or Without Paclitaxel in Stage IVB, Recurrent, or Persistent
Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study. Journal of Clinical Oncology, 22(15), 3113–3119. https://doi.org/10.1200/JCO.2004.04.170
n=280

GOG-169: Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent,
or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group
study.
ORR (%)
median PFS (mo)
Cisplatin
36*
4.8*
2.8*
8.8
median OS (mo)
Paclitaxel + Cisplatin
19*
9.7
n=280

radiation therapy
PS 0-2
Cisplatin 50 mg/m(2) every 3 weeks
(CPT)
Cisplatin 50 mg/m(2) day 1 plus
topotecan 0.75 mg/m(2) days 1 to
3 every 3 weeks (CT)Endpoint
OS
GOG-179: Randomized phase III trial of cisplatin with or without topotecan in
carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.
n=294
ORR (%)
median PFS (mo)
Cisplatin
27*
4.6*
2.9*
6.5*
median OS (mo)
Topetecan + Cisplatin
13*
9.4*
n=294

GOG-179: Randomized phase III trial of cisplatin with or without topotecan in
carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.
Long, H. J., Bundy, B. N., Grendys, E. C., Benda, J. A., McMeekin, D. S., Sorosky, J., … Gynecologic Oncology Group Study. (2005). Randomized Phase III Trial of Cisplatin With or Without Topotecan in
Carcinoma of the Uterine Cervix: A Gynecologic Oncology Group Study. Journal of Clinical Oncology, 23(21), 4626–4633. https://doi.org/10.1200/JCO.2005.10.021

GOG-204: Phase III trial of four cisplatin-containing doublet combinations in stage IVB,
recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study.
Monk, B. J., Sill, M. W., McMeekin, D. S., Cohn, D. E., Ramondetta, L. M., Boardman, C. H., … Cella, D. (2009). Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent,
or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study. Journal of Clinical Oncology, 27(28), 4649–4655. https://doi.org/10.1200/JCO.2009.21.8909
radiation therapy
Measurable disease
PS 0-1
Cisplatin + Gemcitabine
Cisplatin + Vinorelbine
Endpoint
OS
n=513
Cisplatin + Topotecan
Cisplatin + Paclitaxel

Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent,
or persistent cervical carcinoma: a Gynecologic Oncology Group study.

radiation therapy
Measurable disease
PS 0-1
Cisplatin + non-paclitaxel (either
vinorelbine, gemcitabine or
topotecan)
Endpoint
OS
n=513

ORR (%)
median PFS (mo)
Cisplatin + Non-paclitaxel doublet
29
5.8*
3.98-4.7*
10.1-10.3
median OS (mo)
23-26
12.9
n=513

Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or
Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial
JCOG0505
Kitagawa, R., Katsumata, N., Shibata, T., Kamura, T., Kasamatsu, T., Nakanishi, T., … Yoshikawa, H. (2015). Paclitaxel Plus Carboplatin Versus
Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. Journal of
Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 33(19), 2129–35.
https://doi.org/10.1200/JCO.2014.58.4391
Metastatic or recurrent
cervical cáncer
≤1 prior platinum
No prior taxane
Paclitaxel plus carboplatin (TC;
paclitaxel 175 mg/m2 over 3 hours
and carboplatin area under curve 5
mg/mL/min on day 1, repeated every
3 weeks).
Paclitaxel plus cisplatin (TP; paclitaxel
135 mg/m2 over 24 hours on day 1
and cisplatin 50 mg/m2 on day 2,
repeated every 3 weeks)
Non-inferiority OS (HR <1.29)
n = 253

Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent
Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505
https://doi.org/10.1200/JCO.2014.58.4391

https://doi.org/10.1200/JCO.2014.58.4391
Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent
Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505

In advanced cervical cancer
paclitaxel plus either carboplatin or
cisplatin is the chemotherapy
backbone of choice

Angiogenesis in
Cervical Cancer

GOG-240: Improved survival with bevacizumab in advanced cervical cancer.
Tewari, K. S., Sill, M. W., Long, H. J., Penson, R. T., Huang, H., Ramondetta, L. M., … Monk, B. J. (2014). Improved Survival with Bevacizumab in Advanced Cervical Cancer. New England Journal of
Medicine, 370(8), 734–743. https://doi.org/10.1056/NEJMoa1309748
Carcinoma of the cervix
Primary stage IVB
Recurrent/Persistent
Measurable disease
GOG PS 0-1
No prior chemotherapy for recurrence
Paclitaxel + Cisplatin
Paclitaxel + Cisplatin +
Bevacizumab
Endpoint
OS
n=452
Paclitaxel + Topetean
Paclitaxel + Topetean +
BevacizumabStratification factors
Stage IVB vs recurrent/persistence
GOG PS
Prior cisplatin exposure as radio sensitizer

GOG-240: Improved survival with bevacizumab in advanced cervical cancer.
Tewari, K. S., Sill, M. W., Long, H. J., Penson, R. T., Huang, H., Ramondetta, L. M., … Monk, B. J. (2014). Improved Survival with Bevacizumab in Advanced Cervical Cancer. New England Journal of
Medicine, 370(8), 734–743. https://doi.org/10.1056/NEJMoa1309748
Carcinoma of the cervix
Primary stage IVB
Recurrent/Persistent
Measurable disease
GOG PS 0-1
No prior chemotherapy for recurrence
Chemotherapy +
Bevacizumab
Endpoint
OS
n=452
Chemotherapy
Stratification factors
Stage IVB vs recurrent/persistence
GOG PS
Prior cisplatin exposure as radio sensitizer

Tewari, K. S., Sill, M. W., Long, H. J., Penson, R. T., Huang, H., Ramondetta, L. M., … Monk, B. J. (2014). Improved Survival with
Bevacizumab in Advanced Cervical Cancer. New England Journal of Medicine, 370(8), 734–743.
https://doi.org/10.1056/NEJMoa1309748
GOG-240: Improved survival with bevacizumab in advanced cervical
cancer.
ORR (%)
median PFS (mo)
Chemotherapy
48^
8.2*
5.9*
13.3*
median OS (mo)
Chemotherapy + Bevacizumab
36*17*
n=452
Bevacizumab increases toxicity:
Hypertension of grade 2 or higher (25% vs. 2%),
Thromboembolic events of grade 3 or higher (8% vs. 1%), and
Gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).

In advanced cervical cancer
chemotherapy plus bevacizumab
improves outcomes, and should be
considered a standard-of-care

Progress in survival in
cervical cancer
0.
4.5
9.
13.5
18.
1989 1997 2002 2004 2005 2009 2013
4.5
9.0
13.5
18.0
1989 2005 2013
GOG-64
GOG-169
GOG-179
GOG-240
Cisplatin
Cisplatin doublets
(Paclitaxel or Topetecan)
Chemotherapy +
Bevacizumab
medianOS(mo)
Year
Adding bevacizumab to chemotherapy improves survival

66
Alexandrov et al., Nature 2013
Schumacher et al, Science 2015
Neoantigen Load and Tumor Types:
Possible use as a biomarker of activity for IO agents

Conclusions
Systemic therapy in cervical cancer
At the beginning
Only surgery and RT available
Today
Chemotherapy +
Bevacizumab in advanced
disease
Cisplatin in
advanced
disease in
early trials
Cisplatin +
RT in locally-
advanced
disease
Cisplatin +
Paclitaxel in
advanced
disease
Cisplatin +
Topotecan
and other
doublets in
advanced
disease
Unresolved
Neoadjuvant and adjuvant chemotherapy in locally-advanced disease
Immunotherapy and targeted therapy in advanced disease

Cis + Pac + Bev
(n=115)
67 (58.3)
HR=0.68 (95% CI, 0.48-0.97)
P=0.0348
Cis + Pac
(n=114)
Events, n (%) 69 (60.5)
Median OS, mos 14.3 17.5
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 12 3624
ProportionSurviving
Months on Study
RR, % 45 (CR, n=9) 50 (CR, n=17)
2-sided P=0.5090
GOG 240 – Bevacizumab Objective
Cisplatin + Paclitaxel Cohort N=229
Presented at ASCO 2013 by: Krishnansu S. Tewari, MD, FACOG, FACS
Tewari KS et al N Engl J Med. 2014 Feb 20;370(8):734-43.

Progress in Survival in Advanced and Recurrent Cervical Cancer
0.
4.5
9.
13.5
18.
1989 1997 2002 2004 2005 2009 2013
• GOG 110 Cisplatin + Ifosfamide
•GOG 149 Cisplatin + Ifosfamide + Bleomycin
 
•GOG 169 Cisplatin + Palitaxel
•GOG 179 Cisplatin + Topotecn
 
Months
Year
GOG 64 Cisplatin



GOG 240 Cisplatin + Palcitaxel + Bevacizumab

Adding Bevacizumab to Chemotherapy Improves Survival

83
Alexandrov et al., Nature 2013
Schumacher et al, Science 2015
Neoantigen Load and Tumor Types:
Possible use as a biomarker of activity for IO agent

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