CERVICAL CANCER

1. CERVICAL CANCER
DR. R. RAJKUMAR D.M.
MEDICAL ONCOLOGIST
VELAMMAL SPECIALITY HOSPITALS

2. TOPICS
 EPIDEMIOLOGY
 METASTATIC/ RECURRENT
 ADJUVANT
 NEOADJUVANT
 TARGETED AGENTS/ IMMUNOTHERAPY
 FUTURE

3. CERVICAL CANCER
• Cervical Cancer is
the second most
common cancer
among women
worldwide.
• Over 500,000 women
worldwide die of
cervical cancer
annually.
• Approximately every
47 minutes a
woman is

6. CERVICAL CANCER AFFECTS WOMEN IN THEIR PRIME
WHEN THEY ARE NEEDED BY THE FAMILY
Rates per 100,000 women per year
Annual number of cases and age-specific incidence rates of cervical cancer in India
. [Accessed on 16th April 2018]
The Incidence
of Cervical
cancer in India
is highest
amongst 40-64
yrs women

7. RECURRENT CERVICAL CANCER
• Advanced disease at presentation: 15-20%
• Persistent/recurrent disease
• Central pelvic disease
• Lymph nodes
• Lung/Liver
• Peritoneal
• Other
Salani. Am J Obstet Gynecol 2011;204(6).

8. OVERALL 5 YEARS SURVIVAL
FOLLOWING THERAPY:
• Stage I -------80%
• Stage II-------50-60%
• Stage III-------30-40%
• Stage IV-------4%

9. STANDARD SYSTEMIC CHEMOTHERAPY
OPTIONS
• Cisplatin doublets are first line
• Median survival is~12months
• Carboplatin (if prior cisplatin with radiation therapy)
Non-platinum doublets may also be used
• Based on prior therapies and toxicities
• Topotec an and paclitaxel
• Gemictabine and docetaxel (SCOTCERV trial)
Kit agawa. J Clin Oncol 2015;33(19). Tewari. N Engl J Med 2014;370(8). Monk. J Clin Oncol 2009; 27(28). Symonds. Gynecol

10. GOG-204: Study Design
Patients (N=434)
 Primary stage 4b or
recurrent/persistent CC
 Measurable disease
 GOG PS 0-1
 No CNS disease
 No prior chemotherapy
(unless CRT)
Randomize
Regimen 1
Paclitaxel 135 mg/m2 over 24 hours and CDDP 50 mg/m2 q3w, 6 cycles
• Monk BJ, et al. J Clin Oncol 2009; 27(28):4649-4655.
10
Regimen 2
Vinorelbine 30 mg/m2 IV bolus day1 and 8 and CDDP 50 mg/m2 q3w, 6 cycles
Regimen 3
Gemcitabine 1000mg/m2 IV day 1 and 8 and CDDP 50 mg/m2 IV day q3w, 6 cycles
Regimen 4
Topotecan 0.75 mg/m2 over 30 min days 1, 2, 3 CDDP 50 mg/m2 IV day 1, q3w, 6
cycles
Quality of life was assessed for all regimens
A Phase III trial to assess the toxicity and efficacy of cisplatin doublet
combinations in advanced and recurrent cervical cancer

11. GOG-204: Results
•Response rates for PC, VC, GC
and TC were 29.1%, 25.9%,
22.3%, and 23.4%.
•Comparable toxicity except for
leukopenia, neutropenia,
infection and alopecia
By Treatment Group
Proportion
Surviving
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
24
Months on Study
0 12 36
Alive DeadTotal
Treatment
CIS+PAC
CIS+VIN
CIS+GEM
CIS+TOP
29 74 103
23 85 108
20 92 112
22 89 111
Survival by Treatment Group
• Monk BJ, et al. J Clin Oncol 2009; 27(28):4649-4655.
11

12. JCOG 0505
R
A
N
D
O
M
I
Z
E*
Standard arm: TP
Paclitaxel 135 mg/m2 24h d1
Cisplatin 50 mg/m2 2h d2
Experimental arm: TC
Paclitaxel 175 mg/m2 3h d1
CarboplatinAUC 5 1h d1
* Balancing factors:
 Tumors outside of the prior
irradiation field
(yes or no)
 PS 0-1 or 2
 SCC or non-SCC
 Institution
Stage IVB, persistent or
recurrent cervical cancer; not
amenable to curative surgery /
radiotherapy
• ClinicalTrials.gov Identifier:NCT00295789
12

13. 1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6
Years after randomization
Proportion
Arm N Events M
[9
e5
d%
ian
C
(m
I]) 1
O
-
y
S
r 2
O
-
y
S
r 3
O
-
y
S
r
TP 123 106 [161.81.3-2m2.9] 72.4% 38.8% 18.3%
TC 121 98 [141.72.5-2m0.3] 67.6% 31.5% 21.3%
HR: 0.994 [90% CI: 0.789-1.253 (<1.29)]
noninferiority one-sided P = .032#
Overall Survival
• Kitagawa R, et al. J Clin Oncol. 2012;30(Suppl): Abstract 5006.
J Clin Oncol. 2015 Jul 1;33(19):2129-35.
13

14. Advanced/Recurrent Cervical Cancer:
A HUGE UNMET CLINICAL NEED!
14
.

15. GOG 240 Schema
National Institutes of Health. http://clinicaltrials.gov/ct2/show/NCT00803062. Accessed 15 January 2018.
Chemo alone
Chemo + bevacizumab
Activated: 4/6/09
Closed to accrual: 1/3/12
Carcinoma of the cervix
• Primary stage IVB
• Recurrent/persistent
• Measureable disease
• GOG PS 0-1
• No prior chemotherapy
for recurrence
(N = 452)
1:1:1:1
I
Paclitaxel 135 or 175 mg/m2 IV
Cisplatin 50 mg/m2 IV
III
Paclitaxel 175 mg/m2 IV
Topotecan 0.75 mg/m2 d1-3
II
Paclitaxel 135 or 175 mg/m2 IV
Cisplatin 50 mg/m2 IV
Bevacizumab 15 mg/kg IV
IV
Paclitaxel 175 mg/m2 IV
Topotecan 0.75 mg/m2 d1-3
Bevacizumab 15 mg/kg IV
q 21 d Rx to PD,
toxicity, CR
Stratification factors:
• Stage IVB vs recurrent/
persistent disease
• Performance status
• Prior cisplatin Rx as radiation-sensitizer
R
A
N
D
O
M
I
Z
E
United States,
Canada & Spain
22

16. GOG-0240: Final OS/PFS
• Tewari KS, et al. N. Engl J Med 2014;370:734-43.
HR: 0.71 (95% CI: 0.54-0.95)
P=0.004
HR: 0.67 (95% CI: 0.54-0.82)
P=0.002
CT (N=225)
Follow up: 20.8 months
CT + Bev
(N=227)
23

17. NCCN GUIDELINES: SYSTEMIC THERAPY FOR
CERVICAL CANCER
• 1. NCCN. NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer. Version 2.2020.
https://www.nccn.org/professionals/physician_gls/PDF/cervical.pdf. Accessed 19 September 2020.
Preferred regimens Other recommended regimens
Chemoradiation Cisplatin, carboplatin if cisplatin intolerant N/A
First-line combinations Cisplatin/paclitaxel/bevacizu
mab
Carboplatin/paclitaxel/bevaci
zumab
Cisplatin/paclitaxel
Carboplatin/paclitaxel
Topotecan/paclitaxel ±
bevacizumab
Cisplatin/topotecan
Possible
first-line
monotherap
y
Cisplatin Carboplatin or paclitaxel
Second-line therapy Pembrolizumab (for PD-L1+ or MSI-
H/dMMR tumors)
Bevacizumab, albumin-bound paclitaxel, docetaxel,
fluorouracil, gemcitabine, ifosfamide, irinotecan, mitomycin,
pemetrexed, topotecan, vinorelbine
Pembrolizumab for TMB-H tumors
Larotrectinib or entrectinib for NTRK+ gene fusion positive
tumors
31

18. Improving OS in Recurrent or
Metastatic Cervical Cancer
How do we move forward?
4
2
0
18
6
8
10
12
16
14
18
1989 1997 2002 2004 2005 2009 2013
GOG 110 Cisplatin + Ifosfamide
GOG 179 Cisplatin + Topotecan
OS
(months)
GOG 149 Cisplatin + Ifosfamide + Bleomycin
GOG 169 Cisplatin + Paclitaxel
GOG 240 Cisplatin + Paclitaxel + Bevacizumab
Year

19. Cediranib (CIRCCa trial)
• Potent inhibitor of VEGF receptor tyrosine
kinases
• Studied with carboplatin and paclitaxel
• Toxicities: Hypertension, diarrhea, febrile neutropenia
Progression free
survival:
Cediranib: 8.1
months
Pla cebo: 6.7months
Overall survival similar
• Cediranib and mTOR inhibitor study ongoing
Symonds. Lancet Oncol 2015;16(15).

20. PARP inhibitors: GOG 76HH
• Involved in detection and repair of DNA repair
• PARP expression iscorrelated with
chemoresistance
• Higher expression of PARPin cervical cancer
cells
• Cisplatin, paclitaxel and veliparib
• Veliparib twice daily x 7 days
• Outcomes
• Response rate 34.5%
• 7% complete response
• Clinical benefit rate of 75%
• 41.4%with stable disease
Thaker/Salani. Annals of Oncol 2016;28(3):505.

21. ADJUVANT THERAPY

22. OUTBACK: Phase III Trial of CRT ± Adjuvant CT in
Women With Locally Advanced Cervical Cancer
CCO Independent Conference Highlights*
of the 2021 Virtual ASCO Annual Meeting, June 4-8, 2021
*

23. Background
 In 2018, cervical cancer was the fourth most common malignancy globally in women with an estimated 570,000
diagnoses and 311,000 deaths1
 Concurrent cisplatin + RT with brachytherapy is SoC for locally advanced cervical cancer2,3
 Treatment with adjuvant CT after concurrent CRT may improve survival4,5
‒ In a 2008 meta-analysis, absolute OS benefit of 19% at 5 yr (HR: 0.46; P = 00002) was reported with
CRT + adjuvant CT using data from 2 randomized clinical trials4
‒ A randomized phase III trial in patients with stage IIB-IVA cervical cancer reported significantly prolonged PFS/OS for
concurrent gemcitabine plus cisplatin and RT plus 2 cycles of adjuvant gemcitabine/cisplatin vs concurrent cisplatin and
RT alone (3-yr PFS rate: 74.4% vs 65.0%)5
 Phase III OUTBACK trial compared efficacy and safety of standard cisplatin-based CRT followed by adjuvant
carboplatin/paclitaxel vs CRT alone in women with locally advanced cervical cancer eligible for CRT with curative
intent6

24. Mileshkin LR, et al. Presented at ASCO Annual Meeting. 4–8 June 2021. LBA3.
OUTBACK: randomized Phase 3 trial of adjuvant chemotherapy
following chemoradiation as primary treatment for locally advanced
cervical cancer compared with chemoradiation alone
Patients with cervical cancer suitable
for chemoradiation with curative
intent:
• FIGO 2008 Stage IB1+LN, IB2, II, IIIB,
IVA
• ECOG 0–2
• Squamous cell carcinoma,
adenocarcinoma or adenosquamous
carcinoma
• No nodal disease above L3/4
Concurrent
chemoradiation
(CRT)
Concurrent
chemoradiation
(CRT)
Adjuvant
chemoradiation
(ACT)
Carboplatin +
paclitaxel
Primary endpoint:
• Overall survival
Secondary endpoints:
• Progression-free survival
• Adverse events
• Sites of disease recurrence
• Radiation protocol compliance
• Patient-reported outcomes
R
N=926
Stratification factors:
• Pelvic or common iliac nodal involvement
• Requirement for extended-field radiotherapy
• FIGO 2008 stage: IB / IIA or IIB or IIIB / IVA
• Age <60 or ≥60 years
• Hospital / site
24
Study schema
1
1

25. OUTBACK: Baseline Characteristics
Mileshkin. ASCO 2021. Abstr LBA3.
Characteristic
CRT Alone
(n = 456)
CRT + ACT
(n = 463)
Median age, yrs (range) 45 (22-88) 46 (21-99)
ECOG PS, n (%)
 0
 1
 2
344 (75)
94 (21)
18 (4)
337 (73)
117 (25)
9 (2)
Race, n (%)
 White
 Black
 Asian
 Aboriginal/Pacific Islander
 Other
326 (72)
68 (15)
22 (5)
11 (2)
28 (6)
337 (73)
53 (11)
31 (7)
13 (3)
29 (6)
Region, n (%)
 Australia and New Zealand
 USA and Canada
 Rest of world
84 (18)
366 (80)
6 (1)
81 (17)
373 (81)
9 (2)
Tobacco smoking, n (%)
 Never
 Current/ex-smoker/unknown
237 (52)
219 (48)
224 (48)
239 (52)
Characteristic
CRT Alone
(n = 456)
CRT + ACT
(n = 463)
Nodal involvement, n (%)
 None
 Pelvic only
 Common iliac only
 Pelvic and common iliac
 Unknown
225 (49)
144 (32)
33 (7)
44 (10)
10 (2)
231 (50)
149 (32)
31 (7)
44 (10)
8 (2)
Extended field planned, n (%)
 No
 Yes
397 (87)
59 (13)
404 (87)
59 (13)
FIGO 2008 stage, n (%)
 IB1 (all node+), IB2, IIA
 IIB
 IIIB or IVA
152 (33)
196 (43)
108 (24)
154 (33)
197 (43)
112 (24)
Histology, n (%)
 Squamous
 Adenocarcinoma
 Adenosquamous
358 (79)
79 (17)
19 (4)
383 (83)
68 (15)
12 (3)
Median max tumor diameter, cm
(range)
5.0 (0-11) 5.0 (0-12)

26. OUTBACK: Treatment Adherence
 Odds of not starting ACT doubled in those
aged >60 yrs and in non-White patients, and
tripled in those not completing CRT
Mileshkin. ASCO 2021. Abstr LBA3.
CRT Adherence, n (%)
CRT Alone
(n = 456)
CRT + ACT
(n = 463)
Cisplatin cycles
 0-3
 4
 5
27 (6)
46 (10)
383 (84)
49 (11)
32 (7)
382 (83)
Median cisplatin dose
intensity, mg/m2/wk
28 28
Mean EBRT dose, Gy 45.6 45.7
EBRT without interruption 417 (92) 418 (92)
Brachytherapy given 429 (95) 426 (94)
RT completed in 8 wk 292 (67) 300 (68)
CRT completed 353 (77) 356 (77)
ACT Adherence, n (%)
CRT + ACT
(n = 463)
No. ACT cycles
 0
 1
 2
 3
 4
102 (22)
23 (5)
29 (6)
24 (5)
285 (62)
4 full carboplatin doses without delay 200 (70)
4 full paclitaxel doses without delay 197 (69)

27. OUTBACK: Key Efficacy Outcomes
ACT did not
significantly
improve PFS or OS
Mileshkin LR, et al. Presented at ASCO Annual Meeting. 4–8 June 2021.LBA3.
27

28. OUTBACK: Conclusions
 In this analysis of the phase III OUTBACK trial, the addition of adjuvant
carboplatin/paclitaxel following concurrent CRT did not improve OS or
PFS vs CRT alone in patients with locally advanced cervical cancer
 Investigators indicate that results do not support addition of adjuvant
carboplatin/paclitaxel after CRT with weekly cisplatin in this setting
‒ Recommend further research into identifying other adjuvant therapies
with greater potential efficacy and tolerability after standard CRT
 Investigators conclude that pelvic CRT with concurrent weekly cisplatin
remains the standard of care
Mileshkin. ASCO 2021. Abstr LBA3.

29. IMMUNOTHERAPY: PD 1 INHIBITORS
• Blocks the intera ction between PD1 and ligands
PDL1&PDL2
• PDL1 expression has been identified in both
cervic al intraepithelial neoplasia and invasive
cancers
Image from Pardoll. Nat Rev Cancer 2012.
Heeren. Mod Path 2016. Meza che. Mod Path 2015

30. Rationale for Immunotherapy in Cervical Cancer:
Cervical Cancer Immunosuppression
Immunosuppression ↔ Invasion
 HPV E6 and E7 induce cascade of cytokines and T-cell signaling (1,2)
 ↑ IL-6
‒ Myelo/monocyte infiltration (3)
‒ Activated fibroblast inflammation (4)
‒ Disables antigen presentation (5)
 Tregs and MDSC infiltration (6)
 PD-L1 upregulation (7)
 All worse with hypoxia, TGFb, ROS
Smola. Ther Adv Vaccines. 2017;5:69.

31. Mutational Burden Compared With Other Tumors
Kidney
clear
cell
Kidney
papillary
Ovary
Prostate
Myeloma
Lymphoma
B-cell
Gliona
low
grade
Breast
Pancreas
Glioblastoma
Neuroblastoma
CLL
Thyroid
Kidney
chromophobe
AML
Medulloblastoma
ALL
Pilocytic
astrocytoma
Head
and
neck
Stomach
Uterus
Liver
Cervix
Melanoma
Lung
squamous
Lung
adenocarcinoma
Bladder
Lung
small
cell
Esophagus
Colorectum
1000
100
10
1.0
0.1
0.01
0.001
Somatic
Mutation
Prevalence
(Number
Mutations
per
Megabase)
Alexandrov LB, et al. Nature. 2013;500(7463):415-421. 27

32. KEYNOTE-028: BACKGROUND
 Effective treatments needed for cervical cancer with progression after first-line therapy
‒ Many pts platinum resistant
‒ Median OS ~ 7 mos with recurrent cervical cancer[1]
‒ Enrollment in clinical trials encouraged[2]
 Pembrolizumab: anti–PD-1 antibody blocks interaction of PD-1 expressed on T-cells with PD-L1 and PD-L2 expressed on
tumors, thus restoring immune surveillance[3]
‒ FDA approved for metastatic melanoma and NSCLC
 KEYNOTE-028: phase Ib multicohort study evaluating safety and efficacy of pembrolizumab in pts with PD-L1+ advanced solid
tumors
‒ Results from cervical cancer cohort are presented[4]

33. KEYNOTE-028: CONCLUSIONS
 Pembrolizumab active in pts with PD-L1+ advanced cervical cancer[1]
‒ Durable responses lasting median of 26 wks
‒ Some responses lasted 1 yr
 Median OS was 9 mos with 6-mo survival rate of 67%
 Safety profile of pembrolizumab in pts with advanced cervical cancer consistent with other tumor
types
‒ No treatment-related grade 4 AEs; no mortality due to treatment
 Multicohort phase II KEYNOTE-158 study under way to further evaluate safety profile and clinical
benefit of pembrolizumab in advanced cervical cancer[2]

34. KEYNOTE-158 Phase II Basket Trial (Update):
Pembrolizumab Monotherapy in Advanced Cervical Cancer
1. Chung. JCO. 2019;37:1470. 2. Chung. SGO 2021. Abstr 41.
FDA Approval June 2018
For patients with cervical cancer who are
PD-L1+ (CPS1 ≥1), MSI-H or dMMR status
 Ongoing, international, multicohort, open-label phase II study
Pembrolizumab 200 mg Q3W
Adult patients with
advanced cervical cancer
that progressed on or
was intolerant to ≥1 line
of standard therapy,
ECOG PS 0-1, tumor sample
for biomarker analysis
(N = 98)
For 2 yr or until
unacceptable
toxicity, progression,
or withdrawal
 Primary endpoint: ORR per RECIST v1.1
(per independent central review)
‒ Previous interim analysis showed 12.2%
ORR (0% ORR in PD-L1–negative tumors)
This is an updated analysis of cervical cancer
cohort with median 36.9 mo of follow-up
 Secondary endpoints: DoR, PFS, OS, safety

35. KEYNOTE-158 Update: Efficacy
Parameter
Overall
(N = 98)
PD-L1+
(n = 82)
PD-L1-
(n = 15)
ORR, % (95% CI)
14.3
(8.0-22.8)
17.1
(9.7-27.0)
0
(0-21.8)
Best response, n (%)
 CR
 PR
 SD
5 (5.1)
9 (9.2)
16 (16.3)
5 (6.1)
9 (11.0)
13 (15.9)
0
0
3 (20.0)
 Median time to response: 2.3 mo
(range: 1.6-17.6)
 Median DoR: not reached (range: 3.7-35.2+)
 Ongoing responses: 7/14 (50%) responses
ongoing at data cutoff
Lesion size best change from baseline
0
20
40
60
80
100
-20
-40
-60
-80
-100
PD-L1 positive
PD-L1 negative
PD-L1 unknown
-30%
Change
From
BL
(%)
+20%
Chung. SGO 2021. Abstr 41.

36. US FDA Accelerated Approval of Pembrolizumab
(June 12, 2018)
U.S. FDA Press Release. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm610572.htm.
Accessed March 13, 2019.
Companion
Diagnostic PD-L1
IHC 22C3
CPS≥1
30

37. CheckMate 358: Nivolumab
• Phase I/II of cervical and vulvar cancer patients
• 79% with prior treatment
• 62.5% had PDL1 expression
• Objective response rate was 26.3% in cervix cohort
• Disease control rates 68.4%
• Duration of response not rea ched
• Overall survival of 21.9 months
Naumann RW. J Clin Oncol

38. Adoptive Tcell transfer:
Tumor infiltrating lymphocytes (TILs)therapy
• TILsobtained from resected tumor deposit
• Requires tissue procurement and 4-6 weeks to generate
TILs
• Preceded by lymphocyte depletion therapy; followed
by IL2
• Phase I study of single infusion of TILsselected from HPV E6
and E7reactivity (HPV-TILs)
• Response rates
• 3 of 9 patients had objective response rates
• 2 complete responses (15 and 22 months
duration)
• Phase II study
• Objective response in5/18 cervical cancer patients
28% Stevanovic S.J Clin Oncol 2015;33(14):1543. Stevanovic S.Clin Cancer Res 2019;25(5):1486.

39. Tcell receptor gene therapy
• Tcell receptor against an epitope of HPV16 E6
• Leukapheresis to acquire peripheral blood
mononuclear cells
• Stimulated with anti CD3 and IL2
• Transduced with E6TCRretrovirus.
• After lymphocyte depleting regimen,
Tcells were administered
• 12 patients with HPV 16 positive tumors
• 2 objective responses
• 4 stable disease
• Proof of principle
Doran SL.J Clin Oncol 2019.

40. Other areas of interest
• Monoclonal antibodies
• HuMax®-TF-ADC (Tisotumab vedotin)
• Targeting tissue fa ctor-specific cells
• IMMU-132 (Sa cituzmab govitec an)
• Targeting the TROP-2 antigen
• Va ccines
• TVGV-1 and pNGVL4a /E7 va ccines in premalignant
lesions
• Studies evaluating combination of agents

41. Selected Randomized Phase III Immunotherapy Trials in
Recurrent/Metastatic Cervical Cancer (1L)
Clinicaltrials.gov.
Study
Stratification
Factors
Treatment Arms Estimated N Primary Endpoints
KEYNOTE-826
(NCT03635567)
 Stage
 +/- bev
 PD-L1 status
Platinum-based CT ± pembrolizumab 600 PFS (BICR), OS
BEATcc
(NCT03556839)
 Prior CRT
 Histology
 Chemotherap
y backbone:
cis vs carbo
Atezolizumab + bevacizumab and cisplatin or
carboplatin/paclitaxel
404 OS
FERMATA
(NCT03912415)
 Stage
 +/- bev
 PD-L1 status
 Ethnicity
Platinum-based CT + prolgolimab 316 OS

42. Selected Randomized Phase III ICI Trials in Locally
Advanced Cervical Cancer (1L)
Clinicaltrials.gov.
Study Population Treatment Arms Estimated N Primary Endpoints
CALLA
(NCT03830866)
 FIGO 2009 IB2-IIB node+
 IIIA-IVA any nodal status
 Measurable
RECIST v1.1
 ECOG PS 0-1
CRT ± durvalumab
(for 2 yr)
770 PFS
KEYNOTE-A18
(NCT04221945)
 FIGO 2009 IB2-IIB node+
 IIIA-IVA any nodal status
 Measurable
RECIST v1.1
 ECOG PS 0-1
CRT ± pembrolizumab
(for 2 yr)
980 PFS, OS

43. Cervical Cancer: Summary of Available Treatments
1. NCCN Cervical Cancer Guidelines v1.2021. 2. SEER Cancer Stat Facts: Cervical Cancer. National Cancer Institute. Bethesda, MD.
Early disease
CIN 2/CIN 3
Locally advanced
disease Metastatic disease
Cone biopsy
Cryotherapy
Laser therapy
LEEP
FIGO IA1 FIGO IA2 FIGO IB2 + IIA
Surgery followed by
adjuvant treatment depending
on risk factors
FIGO IB3 /IIB
/IIIB
FIGO IVA FIGO IVB
Chemoradiotherapy
(preferred)
Surgery if feasible
Platinum-based
chemotherapy
+/- bevacizumab
Pembrolizumab (PD-L1+/
MSI-H/dMMR/TMB-H),
larotrectinib for NTRK
gene fusion, bevacizumab,
or single-agent
chemotherapy
Cervical
dysplasia
1L
2L+
44%2
36%2 16%2
Initial diagnosis1
Colposcopy/biopsy

44. Locally advanced
disease
Metastatic disease
Chemoradioimmunotherapy
(preferred)
Platinum-based
chemoimmunotherapy
+/- bevacizumab
LN-145 (lifileucel) TILs
vs
tisotumab vedotin
(?IO combo)
Clinical trial
assay-directed
chemotherapy
Recurrent disease
(post-CRT +/- IO)
Prior IO
No prior IO
Platinum-based
chemoimmunotherapy
+/- bevacizumab
Platinum-based
chemotherapy
+/- bevacizumab
(?+immuno-combo)
LN-145 (lifileucel) TILs
vs
tisotumab vedotin
(?IO combo)
Clinical trial
assay-directed
chemotherapy
Cemiplimab?
Chemo replacement?
Future Treatment Sequencing

45. 45 |
2020-2030 Acceleration plan towards elimination
The 2030 targets and elimination threshold are subject to revision depending on the outcomes of the
modeling and the WHO approval process
Vision: A world without cervical cancer
Goal: below 4 cases of cervical cancer per 100,000 woman-years
90%
of girls fully vaccinated
with HPV vaccine by 15
years of age
70%
of women screened with
an HPV test at 35 and 45
years of age and 90%
managed appropriately
30%
reduction in mortality
from cervical cancer
2030
TARGETS

46. The way to get
started is to quit talking
and begin doing.
Walt Disney
Presentation title 20XX 46

47. Summary
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48. Thank you
DR. R. RAJKUMAR
9677722024
drraj12319@gmail.com
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