NCCN Guidelines for Ovarian Cancer V.1.

2021 – Annual on 10/16/20

Guideline Page Institution Vote

Panel Discussion/References
and Request YES NO ABSTAIN ABSENT

OV-5 Based on review of the data and discussion, 24 0 0 7

Internal request:
For patients with germline or somatic BRCA1/2 mutation who
did not receive bevacizumab as part of primary therapy, revise
“Observe (if CR)” option to convey that maintenance therapy
with a PARP inhibitor (olaparib or niraparib) is preferred for
most patients in this category.
OV-5/OV-B
the panel agreed to revise “Observe (if CR)” to
“Consider observation for stage II only” in this
setting.
References:
• Gonzalez-Martin A, Pothuri B, Vergote I, et
al. Niraparib in patients with newly
diagnosed advanced ovarian cancer. N Engl
J Med 2019;381:2391-2402.
• Moore K, Colombo N, Scambia G, et al.
Maintenance olaparib in patients with newly
diagnosed advanced ovarian cancer. N Engl
J Med 2018;379:2495-2505.
• Niraparib (Zejula) [package insert].
https://www.accessdata.fda.gov/drugsatfda_
docs/label/2020/208447s015s017lbledt.pdf.
Revised April 2020. Accessed March 12,
2021.
OV-5

External request: Based on review of the data and discussion, 0 24 0 7

Submission from Astra Zeneca on 05/15/20 to consider
multiple requests:
OV-5:
• Under POST-PRIMARY TREATMENT, switch second
column (bevacizumab therapy) and third column
(testing). Rationale: based on the FDA approval, the
tumor mutation profile guides treatment decision
rather than bevacizumab use.
• Under POST-PRIMARY TREATMENT, within existing
third column (after ‘Bevacizumab used as part of
primary therapy’ section), revise ‘BRCA1/2 wild-type
the panel did not support any of the following:
• Switching the second column
(bevacizumab therapy) and third column
(testing).
• Using the terminology “HRD positive”,
“HRD negative”, and “non-BRCA1/2
mutation”
• Adding “Select patients for therapy based
on FDA-approved companion
diagnostic…”
Based on a review of the data and discussion,
24 0 0 7
the panel consensus supported the following
 NCCN Guidelines for Ovarian Cancer V.1.2021 – Annual on 10/16/20
or unknown’ to “HRD positive and non-BRCA1/2
mutation”
o Within ‘Bevacizumab + olaparib’ under
‘Maintenance Therapy’, include new footnote:
“Select patients for therapy based on an FDA-
approved companion diagnostic for Lynparza”
o Insert a third arrow in this section and add
“HRD negative and non-BRCA1/2 mutation.”
• Under POST-PRIMARY TREATMENT, within existing
third column, after ‘No Bevacizumab used as part of
primary therapy’ section, revise BRCA1/2 wild-type or
unknown’ to “HRD positive and non-BRCA1/2
mutation” and add olaparib + bevacizumab under
maintenance therapy (based on our indication)
• Within ‘Bevacizumab + olaparib’ under
‘Maintenance Therapy’, include new footnote:
“Select patients for therapy based on an FDA-
approved companion
diagnostic for Lynparza”
• Insert a third arrow in this section and add “HRD
negative and non-BRCA1/2 mutation.”
OV-B (1 of 3)
• Under “Tumor molecular analysis as clinically
indicated:”, revise third bullet to, “Test for homologous
recombination deficiency by evaluating for genomic
instability.”
• Under “Tumor molecular analysis as clinically
indicated:” insert in fourth bullet, “can be considered at
the treating physician’s or pathologist’s discretion”
OV-5/OV-C
External request:
Submission from Myriad on 05/21/20, revised on 09/08/20, to
consider multiple requests:
changes on the pathway for bevacizumab
used as part of primary therapy, BRCA1/2
wildtype or unknown and CR/PR: Added
branches to differentiate the maintenance
therapy options for "HR proficient or status
unknown" and "HR deficient".
• If HR proficient/status unknown:
Bevacizumab
• If HR deficient: Bevacizumab +
olaparib
The panel consensus did not support the
addition of “olaparib + bevacizumab” as a 0 24 0 7
maintenance therapy option in the ‘No
Bevacizumab used as part of primary therapy’
section, based on limited available data.
OV-B (1 of 3)
Based on a review of the data and discussion, 0 24 0 7
the panel did not use the language proposed
in the submission. However, the panel
supported adding the following language: In
addition to BRCA1/2 testing, other methods
for evaluating homologous recombination
status (genomic instability, loss of
heterozygosity) can be considered.
See Submission for references.
OV-5
Bevacizumab + olaparib was already listed as
a maintenance therapy option for patients with
 NCCN Guidelines for Ovarian Cancer V.1.2021 – Annual on 10/16/20
• OV-5: In the decision tree on page OV-5, for women
who have received bevacizumab as part of their
primary therapy, we recommend that an indication be
added that shows the utilization of bevacizumab +
olaparib is now based on a BRCA1/2 mutation and/or
genomic instability. A new footnote can also be added
to state genomic instability as defined by Myriad
myChoice® CDx.
• OV-C (7 of 10): Please change footnote O to include
the underlined: “For patients treated with three or
more prior chemotherapy regimens and whose cancer
is associated with HRD defined by either: 1)
deleterious or suspected deleterious BRCA mutation;
or 2) genomic instability as defined by Myriad
myChoice® CDx and progression >6 months after
response to the last platinum-based chemotherapy.”
OV-5
External request:
Submission from GSK on 05/19/20 to consider the addition of
niraparib + bevacizumab as targeted combination for patients
who had a complete or partial response to front-line platinum-
based chemotherapy + bevacizumab, and who have either
germline or somatic BRCA1/2 mutations or are BRCA1/2 wild-
type or unknown.
OV-5, OV-C 5 of 10
External request:
Submission from Blueprint Medicines on 09/10/20 to consider
adding “RET therapy for RET fusion-positive tumors:
pralsetinib” on OV-5, Post Primary Treatment, and on OV-C 5
of 10, within “Useful in Certain Circumstances.”
CR/PR and a BRCA1/2 mutation who had
bevacizumab as part of primary therapy.
Based on a review of the FDA indication and
discussion, the panel consensus was to 24 0 0 7
modify the pathway for patients who received
bevacizumab as part of primary therapy, have
CR/PR and BRCA1/2 wild-type or unknown,
such that bevacizumab + olaparib is a
maintenance option only for those who have
HR deficient tumors.
OV-C (7 of 10) 0 24 0 7
Based on a review of the data and discussion,
the panel consensus did not support these
specific revisions to the Guidelines regarding
the definition of HRD.
See Submission for references.
Based on a review of the data and discussion, 0 24 0 7
the panel consensus did not support the
addition of these specific recommendations
into the Guidelines due to insufficient available
data.
See Submission for references.
Based on a review of the data and discussion, 0 24 0 7
the panel consensus did not support the
addition of these specific recommendations
into the Guidelines due to insufficient available
data.
See Submission for references.
 NCCN Guidelines for Ovarian Cancer V.1.2021 – Annual on 10/16/20
OV-7
External request:
Submission from Clovis Oncology on 05/15/20 to consider
these requests:
• Downgrade “Observe” from category 2A to 2B or
3 and that “observe” should only be considered for
patients who cannot be treated with PARP
inhibitors
• Update the PARP inhibitor class [for maintenance]
from category 2A to category 1 in recurrent
ovarian cancer given the consistent data across
three randomized controlled phase 3 trials in the
setting of recurrent ovarian cancer.
Based on a review of the data and discussion, 3 21 0 7
the panel consensus did not support changing
the category of evidence for the Observe
option.
Based on the review of the data in the noted
24 0 0 7
references the panel consensus was that the
use of maintenance PARP inhibitor therapy
(ie. niraparib, olaparib, or rucaparib) is
supported by high-level evidence for BRCA1/2
mutation carriers with CR/PR after
combination platinum-based chemotherapy for
recurrent platinum-sensitive disease, provided
they have not previously received PARPi
treatment, and the category was changed
from a category 2A to a category 1
recommendation for this indication.
References:
• SOLO2:
o Pujade-Lauraine E, Ledermann JA,
Selle F, et al. Olaparib tablets as
maintenance therapy in patients with
platinum-sensitive, relapsed ovarian
cancer and a BRCA1/2 mutation
(SOLO2/ENGOT-Ov21): a double-blind,
randomised, placebo-controlled, phase
3 trial. Lancet Oncol 2017;18:1274-
1284.
• ARIEL3:
o Ledermann JA, Oza AM, Lorusso D, et
al. Rucaparib for patients with platinum-
sensitive, recurrent ovarian carcinoma
(ARIEL3): post-progression outcomes
and updated safety results from a
NCCN Guidelines for Ovarian Cancer V.1.2021 – Annual on 10/16/20

randomised, placebo-controlled, phase

3 trial. Lancet Oncol 2020;21:710-722.
o Coleman RL, Oza AM, Lorusso D, et al.
Rucaparib maintenance treatment for
recurrent ovarian carcinoma after
response to platinum therapy (ARIEL3):
a randomised, double-blind, placebo-
controlled, phase 3 trial. Lancet
2017;390:1949-1961.
• Study 19:
o Friedlander M, Matulonis U, Gourley C,
et al. Long-term efficacy, tolerability and
overall survival in patients with platinum-
sensitive, recurrent high-grade serous
ovarian cancer treated with
maintenance olaparib capsules following
response to chemotherapy. Br J Cancer
2018;119:1075-1085.
• NOVA
o Mirza MR, Monk BJ, Herrstedt J, et al.
Niraparib maintenance therapy in
platinum-sensitive, recurrent ovarian
cancer. N Engl J Med 2016;375:2154-
2164.
o Mirza MR, Benigno B, Dorum A, et al.
Long-term safety in patients with
recurrent ovarian cancer treated with
niraparib versus placebo: Results from
the phase III ENGOT-OV16/NOVA trial.
Gynecol Oncol 2020;159:442-448.
o Del Campo JM, Matulonis UA, Malander
S, et al. Niraparib Maintenance Therapy
in Patients With Recurrent Ovarian
Cancer After a Partial Response to the
Last Platinum-Based Chemotherapy in
the ENGOT-OV16/NOVA Trial. J Clin
Oncol 2019:JCO1802238.
 NCCN Guidelines for Ovarian Cancer V.1.2021 – Annual on 10/16/20
LCOC-2/LCOC-3
Internal request:
Comment to clarify whether PARP inhibitor maintenance
therapy options on OV-5 can be considered (post-primary
therapy) for those with stage II-IV epithelial less common
ovarian cancers (carcinosarcoma, clear cell carcinoma,
mucinous carcinoma, grade 1 endometrioid, low-grade
serous).
Based on a review of the data and discussion, 24 0 0 7
the panel consensus supported that the PARP
inhibitor maintenance therapy options on OV-
5 (post-primary therapy) could be considered
for those with stage II-IV carcinosarcoma or
clear cell carcinoma of the ovary, if known
BRCA1/2 mutation.
The following footnote was included on OV-5:
Post-primary treatment recommendations for
stage II-IV high-grade serous or grade 2/3
endometrioid carcinoma; consider for clear
cell carcinoma or carcinosarcoma with a
BRCA1/2 mutation.
Panel consensus did not support that
maintenance therapy options on OV-5 could
be considered for patients with mucinous
carcinoma, grade 1 endometrioid, low-grade
serous, or BRCA1/2 wild-type carcinosarcoma
or clear cell carcinoma.
References:
• Gonzalez-Martin A, Pothuri B, Vergote I, et
al. Niraparib in patients with newly
diagnosed advanced ovarian cancer. N Engl
J Med 2019;381:2391-2402.
• Moore K, Colombo N, Scambia G, et al.
Maintenance olaparib in patients with newly
diagnosed advanced ovarian cancer. N Engl
J Med 2018;379:2495-2505.
• Ray-Coquard I, Pautier P, Pignata S, et al.
Olaparib plus bevacizumab as first-line
maintenance in ovarian cancer. N Engl J
Med 2019;381:2416-2428. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/31851
799.
 NCCN Guidelines for Ovarian Cancer V.1.2021 – Annual on 10/16/20

LCOC-5/LCOC-6 Based on the discussion, the panel consensus 24 0 0 7

Internal request:
Comment to include the following options for stage IC grade I
endometrioid/low-grade serous carcinoma:
• Following adjuvant chemotherapy: Maintenance
hormonal therapy (category 2B) or Observe
was to include the following options for stage
IC grade I endometrioid/low-grade serous
carcinoma:
• Following adjuvant chemotherapy:
Maintenance hormonal therapy
(category 2B; including anastrozole,
letrozole, emestane, leuprolide
acetate, tamoxifen) or Observe