Subject: Opdivo 1894-A SGM P2023b
Policy:
I. INDICATIONS
The indications below including FDA-approved indications and
compendial uses are considered a covered benefit provided that
all the approval criteria are met and the member has no
exclusions to the prescribed therapy.
A. FDA-Approved Indications
1. Unresectable or Metastatic Melanoma
Opdivo, as a single agent or in combination with
ipilimumab, is indicated for the treatment of adult and
pediatric patients 12 years and older with unresectable or
metastatic melanoma.
2. Adjuvant Treatment of Melanoma
Opdivo is indicated for the adjuvant treatment of adult
and pediatric patients 12 years and older with completely
resected stage IIB, stage IIC, stage III, or stage IV
melanoma.
3. Metastatic Non-Small Cell Lung Cancer
a. Opdivo, in combination with ipilimumab, is indicated
for the first-line treatment of adult patients with
metastatic non-small cell lung cancer (NSCLC) whose
tumors express PD-L1 (≥1%) as determined by an
FDA-approved test, with no EGFR or ALK genomic
tumor aberrations.
b. Opdivo, in combination with ipilimumab and 2 cycles
of platinum-doublet chemotherapy, is indicated for the
first-line treatment of adult patients with metastatic or
recurrent NSCLC, with no EGFR or ALK genomic tumor
aberrations.
c. Opdivo is indicated for the treatment of adult patients
with metastatic NSCLC with progression on or after
platinum-based chemotherapy. Patients with EGFR or
ALK genomic tumor aberrations should have disease
progression on FDA-approved therapy for these
aberrations prior to receiving Opdivo.
4. Neoadjuvant Treatment of Resectable Non-Small Cell
Lung Cancer
Opdivo, in combination with platinum-doublet
chemotherapy, is indicated as neoadjuvant treatment of
adult patients with resectable (tumors ≥4 cm or node
positive) non-small cell lung cancer (NSCLC).
5. Malignant Pleural Mesothelioma
Opdivo, in combination with ipilimumab, is indicated for
the first-line treatment of adult patients with unresectable
malignant pleural mesothelioma.
6. Advanced Renal Cell Carcinoma
a. Opdivo as a single agent is indicated for the treatment
of adult patients with advanced renal cell carcinoma
(RCC) who have received prior anti-angiogenic
therapy.
b. Opdivo, in combination with ipilimumab, is indicated
for the first-line treatment of adult patients with
intermediate or poor risk advanced RCC.
c. Opdivo, in combination with cabozantinib, is indicated
for the first-line treatment of adult patients with
advanced RCC.
7. Classical Hodgkin Lymphoma
Opdivo is indicated for the treatment of adult patients
with classical Hodgkin lymphoma (cHL) that has relapsed
or progressed after:
a. Autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin, or
b. Three or more lines of systemic therapy that includes
autologous HSCT.
8. Squamous Cell Carcinoma of the Head and Neck
Opdivo is indicated for the treatment of adult patients
with recurrent or metastatic squamous cell carcinoma of
the head and neck (SCCHN) with disease progression on
or after platinum-based therapy.
9. Urothelial Carcinoma
a. Opdivo is indicated for the adjuvant treatment of adult
patients with urothelial carcinoma (UC) who are at
high risk of recurrence after undergoing radical
resection of UC.
b. Opdivo is indicated for the treatment of adult patients
with locally advanced or metastatic urothelial
carcinoma who:
i. Have disease progression during or following
platinum-containing chemotherapy
ii. Have disease progression within 12 months of
neoadjuvant or adjuvant treatment with
platinum-containing chemotherapy.
10. Microsatellite Instability-High or Mismatch Repair
Deficient Metastatic Colorectal Cancer
Opdivo, as a single agent or in combination with
ipilimumab, is indicated for the treatment of adult and
pediatric patients 12 years and older with microsatellite
instability-high (MSI-H) or mismatch repair deficient
(dMMR) metastatic colorectal cancer (CRC) that has
progressed following treatment with a fluoropyrimidine,
oxaliplatin, and irinotecan.
11. Hepatocellular Carcinoma
Opdivo, in combination with ipilimumab, is indicated for
the treatment of adult patients with hepatocellular
carcinoma (HCC) who have been previously treated with
sorafenib.
12. Esophageal Carcinoma
a. Opdivo is indicated for the adjuvant treatment of
completely resected esophageal or gastroesophageal
junction cancer with residual pathologic disease in
adult patients who have received neoadjuvant
chemoradiotherapy (CRT).
b. Opdivo, in combination with fluoropyrimidine- and
platinum-containing chemotherapy, is indicated for
the first-line treatment of adult patients with
unresectable advanced or metastatic esophageal
squamous cell carcinoma (ESCC).
c. Opdivo, in combination with ipilimumab, is indicated
for the first-line treatment of adult patients with
unresectable advanced or metastatic esophageal
squamous cell carcinoma (ESCC).
d. Opdivo is indicated for the treatment of adult
patients with unresectable advanced, recurrent or
metastatic esophageal squamous cell carcinoma
(ESCC) after prior fluoropyrimidine- and platinum-
based chemotherapy.
13. Gastric Cancer, Gastroesophageal Junction Cancer,
Esophageal Adenocarcinoma
Opdivo, in combination with fluoropyrimidine- and
platinum-containing chemotherapy, is indicated for the
treatment of adult patients with advanced or metastatic
gastric cancer, gastroesophageal junction cancer, and
esophageal adenocarcinoma.
B. Compendial Uses
1. Cutaneous melanoma
2. Non-small cell lung cancer
3. Renal cell carcinoma
4. Classical Hodgkin lymphoma
5. Head and neck cancers
6. Urothelial carcinoma
a. Bladder cancer
b. Primary carcinoma of the urethra
c. Upper genitourinary tract tumors
d. Urothelial carcinoma of the prostate
7. Colorectal cancer, including appendiceal adenocarcinoma
and anal adenocarcinoma
8. Hepatocellular carcinoma
9. Uveal Melanoma
10. Anal Carcinoma
11. Merkel Cell Carcinoma
12. Central Nervous System (CNS) brain metastases
13. Gestational trophoblastic neoplasia
14. Malignant pleural mesothelioma
15. Malignant peritoneal mesothelioma
16. Small bowel adenocarcinoma
17. Ampullary Adenocarcinoma
18. Extranodal NK/T-cell lymphoma
19. Endometrial Carcinoma
20. Vulvar Cancer
21. Gastric Cancer
22. Esophageal/Esophagogastric Junction Cancers
23. Small cell lung cancer
24. Cervical Cancer
25. Pediatric Diffuse High-Grade Gliomas
26. Pediatric Primary Mediastinal Large B-cell Lymphoma
27. Kaposi Sarcoma
28. Bone Cancer
29. Biliary Tract Cancers
a. Cholangiocarcinoma
b. Gallbladder Cancer
30. Soft Tissue Sarcoma
a. Extremity/body wall sarcoma
b. Head/neck sarcoma
c. Retroperitoneal/intra-abdominal sarcoma
d. Rhabdomyosarcoma
e. Angiosarcoma
All other indications are considered experimental/investigational
and not medically necessary.
II. DOCUMENTATION
Submission of the following information is necessary to initiate
the prior authorization review:
A. Documentation of laboratory report confirming MSI-H or
mismatch repair deficient (dMMR) tumor status, where
applicable.
B. Documentation of programmed death ligand 1 (PD-L1) tumor
expression, where applicable.
C. Documentation of the presence of EGFR exon 19 deletions or
exon 21 L858R mutations or ALK rearrangements, where
applicable.
III. EXCLUSIONS
Coverage will not be provided for members who have
experienced disease progression while on programmed death
receptor-1 (PD-1) or programmed death ligand 1 (PD-L1)
inhibitor therapy (other than when used as second-line or
subsequent therapy for metastatic or unresectable melanoma in
combination with ipilimumab following progression on single
agent anti-PD-1 immunotherapy).
IV. CRITERIA FOR INITIAL APPROVAL
A. Cutaneous Melanoma
Authorization of 6 months may be granted for treatment of
cutaneous melanoma in either of the following settings:
1. The requested medication will be used as a single agent
or in combination with ipilimumab (4 doses of ipilimumab,
followed by Opdivo as a single agent) for locally
recurrent, unresectable, progressive or metastatic
disease.
2. The requested medication will be used as a single agent
or in combination with ipilimumab (4 doses of ipilimumab,
followed by Opdivo as a single agent) as adjuvant
treatment of stage III or IV disease following complete
resection or no evidence of disease.
3. The requested medication will be used as a single agent
as adjuvant treatment of stage IIB and IIC disease
following complete resection.
B. Non-Small Cell Lung Cancer (NSCLC)
1. Authorization of 6 months may be granted for treatment
of recurrent, advanced or metastatic non-small cell lung
cancer if either of the following criteria are met:
a. There are no EGFR exon 19 deletions or exon 21
L858R mutations or ALK rearrangements (unless
testing is not feasible due to insufficient tissue) and
the requested medication will be used in a regimen
containing ipilimumab.
b. The requested medication will be used as single agent
subsequent therapy.
2. Authorization of 3 months (for up to 3 cycles total) may
be granted for neoadjuvant treatment of resectable non-
small cell lung cancer (NSCLC) in combination with
platinum-doublet chemotherapy.
C. Renal Cell Carcinoma
Authorization of 6 months may be granted for treatment of
relapsed, advanced, or stage IV renal cell carcinoma, in any
of the following settings:
1. The requested medication will be used as a single agent
for clear cell histology as subsequent therapy.
2. The requested medication will be used as a single agent
for non-clear cell histology.
3. The requested medication will be used in combination
with ipilimumab (4 doses of ipilimumab, followed by
Opdivo as a single agent) for disease with clear cell
histology as:
a. First-line therapy for poor or intermediate risk.
b. First-line therapy for favorable risk.
c. Subsequent therapy.
4. The requested medication will be used in combination
with cabozantinib.
D. Classical Hodgkin Lymphoma (cHL)
Authorization of 6 months may be granted for treatment of
classical Hodgkin lymphoma when either of the following
criteria is met:
1. The requested medication will be used as palliative or
subsequent therapy and the member meets any of the
following criteria:
a. Member has relapsed or progressed after high-dose
therapy and autologous stem cell rescue (HDT/ASCR).
b. Member has relapsed or refractory disease and is
transplant-ineligible.
c. Member has relapsed or refractory disease and was
either heavily pretreated or there was a decrease in
cardiac function.
d. Member is post-allogeneic transplant
2. The requested medication will be used in combination
with brentuximab vedotin or in combination with ICE
(ifosfamide, carboplatin, etoposide) for relapsed or
refractory disease.
3. The requested medication will be used as a single agent
for disease refractory to at least three lines of prior
therapy.
E. Head and Neck Cancers
Authorization of 6 months may be granted for treatment of
head and neck cancers in members who meet either of the
following criteria:
1. For unresectable, recurrent, persistent or metastatic
disease.
2. For nasopharyngeal cancer in combination with cisplatin
and gemcitabine for unresectable, recurrent, persistent or
metastatic disease.
F. Urothelial Carcinoma – Bladder Cancer
Authorization of 6 months may be granted as a single agent
for treatment of bladder cancer when any of the following
conditions are met:
1. As subsequent therapy for locally advanced, recurrent,
persistent, or metastatic disease.
2. As adjuvant therapy in members who are at high risk of
recurrence after undergoing resection.
G. Urothelial Carcinoma – Primary Carcinoma of the
Urethra
Authorization of 6 months may be granted as a single agent
for treatment of primary carcinoma of the urethra when
either of the following are met:
1. As subsequent therapy for recurrent, locally advanced, or
metastatic disease.
2. As adjuvant therapy in members who are at high risk of
recurrence after undergoing resection.
H. Urothelial Carcinoma – Upper Genitourinary Tract
Tumors or Urothelial Carcinoma of the Prostate
Authorization of 6 months may be granted as a single agent
for treatment of upper genitourinary (GU) tract tumors or
urothelial carcinoma of the prostate when either of the
following are met:
1. As subsequent therapy for locally advanced or metastatic
disease.
2. As adjuvant therapy in members who are at high risk of
recurrence after undergoing resection.
I. Colorectal Cancer
Authorization of 6 months may be granted for treatment of
colorectal cancer, including appendiceal adenocarcinoma and
anal adenocarcinoma, for microsatellite-instability high (MSI-
H) or mismatch repair deficient (dMMR) tumors when used
as a single agent or in combination with ipilimumab (4 doses
of ipilimumab, followed by Opdivo as a single agent) for
advanced, metastatic, unresectable, or inoperable disease.
J. Small Bowel Adenocarcinoma
Authorization of 6 months may be granted as a single agent
or in combination with ipilimumab for treatment of advanced
or metastatic small bowel adenocarcinoma for microsatellite-
instabilty high (MSI-H) or mismatch repair deficient (dMMR)
tumors.
K. Ampullary Adenocarcinoma
Authorization of 6 months may be granted in combination
with ipilimumab for treatment of progressive, unresectable,
or metastatic microsatellite instability-high (MSI-H) or
mismatch repair deficient (dMMR) ampullary
adenocarcinoma.
L. Hepatocellular Carcinoma
Authorization of 6 months may be granted as a single agent
or in combination with ipilimumab (4 doses of ipilimumab,
followed by Opdivo as a single agent) for treatment of
hepatocellular carcinoma.
M. Uveal Melanoma
Authorization of 6 months may be granted as a single agent
or in combination with ipilimumab for treatment of uveal
melanoma for unresectable or metastatic disease.
N. Anal Carcinoma
Authorization of 6 months may be granted as a single agent
for subsequent treatment of metastatic anal carcinoma.
O. Merkel Cell Carcinoma
Authorization of 6 months may be granted for treatment of
Merkel cell carcinoma in either of the following settings:
1. Metastatic disease.
2. Neoadjuvant treatment of node positive disease.
3. Progressive, unresectable, recurrent, or stage IV disease
when used in combination with ipilimumab.
P. CNS Brain Metastases
Authorization of 6 months may be granted for treatment of
CNS brain metastases when either of the following criteria
are met:
1. The requested medication will be used as a single agent
or in combination with ipilimumab in members with
melanoma.
2. The requested medication will be used as a single agent
in members with PD-L1 positive non-small cell lung
cancer.
Q. Gestational Trophoblastic Neoplasia
Authorization of 6 months may be granted as a single agent
for treatment of gestational trophoblastic neoplasia for
multiagent chemotherapy-resistant disease when either of
the following criteria is met:
1. Member has recurrent or progressive intermediate
trophoblastic tumor (placental site trophoblastic tumor or
epithelioid trophoblastic tumor) following treatment with
a platinum-based regimen.
2. Member has high-risk disease.
R. Malignant Pleural or Peritoneal Mesothelioma
Authorization of 6 months may be granted for the treatment
of malignant pleural or peritoneal mesothelioma, including
pericardial mesothelioma and tunica vaginalis testis
mesothelioma, in either of the following settings:
1. The requested medication will be used as first line
therapy in combination with ipilimumab.
2. The requested medication will be used as subsequent
therapy as a single agent or in combination with
ipilimumab.
S. Esophageal and Esophagogastric Junction Carcinoma
1. Authorization of 6 months may be granted for treatment
of esophageal or esophagogastric junction in members
who are not surgical candidates or have unresectable
locally advanced, recurrent or metastatic disease when
the requested medication will be used in combination with
ipilimumab or fluoropyrimidine and platinum containing
chemotherapy or will be used as subsequent therapy.
2. Authorization of 6 months may be granted for adjuvant
treatment of completely resected esophageal or
esophagogastric junction cancer with residual pathologic
disease.
3. Authorization of 6 months may be granted as a single
agent or in combination with ipilimumab for neoadjuvant
or perioperative treatment of esophageal or
esophagogastric junction adenocarcinoma if tumor is
microsatellite instability-high (MSI-H) or mismatch repair
deficient (dMMR) and member is medically fit for surgery.
T. Extranodal NK/T-Cell Lymphoma
Authorization of 6 months may be granted for treatment of
relapsed or refractory extranodal NK/T-cell lymphoma.
U. Endometrial Carcinoma
Authorization of 6 months may be granted as a single agent
for subsequent treatment of recurrent or metastatic
microsatellite instability-high (MSI-H) or mismatch repair
deficient (dMMR) endometrial carcinoma.
V. Vulvar Cancer
Authorization of 6 months may be granted for treatment of
HPV-related advanced, recurrent, or metastatic vulvar cancer
as subsequent therapy as a single agent.
W. Gastric Cancer
Authorization of 6 months may be granted for treatment of
gastric cancer in any of the following settings:
1. When the requested medication is being used in members
who are not surgical candidates or have unresectable
locally advanced, recurrent, or metastatic disease, when
the requested medication will be used in combination with
ipilimumab or chemotherapy.
2. When the requested medication will be used as a single
agent or in combination with ipilimumab for neoadjuvant
or perioperative treatment of gastric adenocarcinoma if
tumor is microsatellite instability-high (MSI-H) or
mismatch repair deficient (dMMR) and member is
medically fit for surgery
X. Small Cell Lung Cancer
Authorization of 6 months may be granted for subsequent
treatment of relapsed or progressive small cell lung cancer as
a single agent.
Y. Cervical Cancer
Authorization of 6 months may be granted for subsequent
treatment of recurrent or metastatic cervical cancer as a
single agent if PD-L1 positive (combined positive score [CPS]
≥1).
Z. Pediatric Diffuse High-Grade Gliomas
Authorization of 6 months may be granted for hypermutant
tumor pediatric diffuse high-grade glioma as adjuvant
treatment or for recurrent or progressive disease.
AA. Pediatric Primary Mediastinal Large B-Cell Lymphoma
Authorization of 6 months may be granted as a single agent
or in combination with brentuximab vedotin for treatment of
relapsed or refractory primary mediastinal large B-cell
lymphoma.
BB. Kaposi Sarcoma
Authorization of 6 months may be granted in combination
with ipilimumab for subsequent treatment of
relapsed/refractory classic Kaposi Sarcoma.
CC. Bone Cancer
Authorization of 6 months may be granted in combination
with ipilimumab for unresectable or metastatic disease when
all of the following are met:
1. Disease has tumor mutation burden-high (TMB-H) [≥10
mutations/megabase (mut/Mb)] tumors
2. Disease has progressed following prior treatment and has
no satisfactory alternative treatment options
DD. Biliary Tract Cancers (Cholangiocarcinoma and
Gallbladder Cancer)
Authorization of 6 months may be granted as subsequent
treatment in combination with ipilimumab for unresectable or
resected gross residual (R2) disease, or metastatic disease
that is tumor mutation burden-high (TMB-H).
EE. Soft Tissue Sarcoma
Authorization of 6 months may be granted for treatment of
soft tissue sarcoma in the following settings:
1. The requested medication will be used as a single agent
or in combination with ipilimumab for treatment of
extremity/body wall sarcomas, head/neck sarcomas and
retroperitoneal/intra-abdominal sarcomas and
rhabdomyosarcoma.
2. The requested medication will be used in combination
with ipilimumab for the treatment of angiosarcoma.
V. CONTINUATION OF THERAPY
A. Adjuvant treatment of melanoma or urothelial
carcinoma
Authorization of 6 months may be granted (up to 12 months
total) for continued treatment in members requesting
reauthorization for cutaneous melanoma or urothelial
carcinoma who have not experienced disease recurrence or
an unacceptable toxicity.
B. Non-small cell lung cancer or Malignant pleural
mesothelioma
Authorization of 6 months may be granted (up to 24 months
total when used in combination with ipilimumab) for
continued treatment in members requesting reauthorization
for non-small cell lung cancer or malignant pleural, including
pericardial mesothelioma and tunica vaginalis testis
mesothelioma subtypes, when there is no evidence of
unacceptable toxicity or disease progression while on the
current regimen. Neoadjuvant treatment of NSCLC will be
approved for a total of 3 months of therapy.
C. Renal Cell Carcinoma
Authorization of 6 months may be granted (up to 24 months
total when used in combination with cabozantinib) for
continued treatment in members requesting reauthorization
for renal cell carcinoma when there is no evidence of
unacceptable toxicity or disease progression while on the
current regimen.
D. Gastric Cancer, Esophageal Cancer,
and Esophagogastric Junction Carcinoma
Authorization of 6 months may be granted for continued
treatment in members requesting reauthorization for gastric
cancer, esophageal cancer, and esophagogastric junction
carcinoma when there is no evidence of unacceptable toxicity
or disease progression while on the current regimen for the
following durations of therapy:
1. Esophageal squamous cell carcinoma in combination with
ipilimumab or chemotherapy for up to 24 months
2. Unresectable advanced, recurrent or metastatic
esophageal squamous cell carcinoma as a single agent
until disease progression or unacceptable toxicity
3. Adjuvant treatment of resected esophageal or
esophagogastric junction cancer as a single agent for up
to 12 months
4. Gastric cancer, esophagogastric junction cancer, and
esophageal adenocarcinoma in combination with
chemotherapy for up to 24 months
E. All other indications
Authorization of 6 months may be granted for continued
treatment in members requesting reauthorization for all
other indications listed in Section IV when there is no
evidence of unacceptable toxicity or disease progression
while on the current regimen.
Place of Service:
Outpatient
The above policy is based on the following references:
- Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; October 2023.
- The NCCN Drugs & Biologics Compendium® © 2023 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed November 3, 2023.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. Version 3.2023. https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf Accessed September 6, 2023
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 2.2023. https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed September 6, 2023
- Lexicomp [database online]. Hudson, OH: Lexi-Comp, Inc.; https://online.lexi.com/lco/action/home [available with subscription]. Accessed September 6, 2023.
Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
December 31, 2023
