1. Invasive Breast Cancer:

a. As single agent or in combination with carboplatin for recurrent unresectable (local or regional) or stage IV (M1) HER2 negative disease that is (NCCN 2A):

i. Hormone receptor-negative; or

ii. Hormone receptor-positive with visceral crisis or endocrine therapy refractory.

b. Third-line therapy and beyond in combination with trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive disease in individuals with recurrent unresectable (local or regional) or stage IV (M1) disease that is (NCCN 2A):

i. Hormone receptor-negative

ii. Hormone receptor-positive with or without endocrine therapy

c. Therapy in combination with pembrolizumab for PD-L1 positive triple negative recurrent unresectable (local or regional) or stage IV (M1) disease:

i. As preferred first-line therapy; (NCCN 1) or

ii. As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used. (NCCN 2A)

d. May be substituted for other taxanes (paclitaxel or docetaxel) in select individuals due to medical necessity (i.e., hypersensitivity reaction). (NCCN 2A)

2. Inflammatory Breast Cancer:

a. Third-line therapy and beyond in combination with trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive disease in individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease that is (NCCN 2A):

i. Hormone receptor-negative

ii. Hormone receptor-positive with or without endocrine therapy

b. Single agent therapy or in combination with carboplatin (useful in certain circumstances, in select individuals with high tumor burden, rapidly progressing disease, and visceral crisis) for individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-negative disease that is (NCCN 2A):

i. Hormone receptor negative.

ii. Hormone receptor-positive with visceral crisis or endocrine therapy refractory.

c. Therapy in combination with pembrolizumab for PD-L1 positive triple negative disease in individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease:

i. As preferred first-line therapy (NCCN 1); or

ii. As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used (NCCN 2A).May be substituted for other taxanes (paclitaxel or docetaxel) in select patients due to medical necessity (i.e., hypersensitivity reaction). (NCCN 2A)

a. Primary treatment for unresectable or metastatic disease in combination with gemcitabine; (NCCN 2A) or

b. Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine. (NCCN 2A)

a. Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine. (NCCN 2A)

a. Primary treatment for unresectable or metastatic disease in combination with gemcitabine (NCCN 2A); or

b. Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine. (NCCN 2A).

a. Subsequent systemic therapy, given alone (no HIV) or with antiretroviral therapy (ART) for people with HIV (PWH), for relapsed/refractory advanced cutaneous, oral, visceral, or nodal disease that has progressed on or not responded to first-line systemic therapy, and progressed on alternate first-line systemic therapy. (NCCN 2A)

a. As a single agent or in combination with carboplatin for metastatic or unresectable disease as second-line or subsequent therapy for disease progression or after maximum clinical benefit from BRAF targeted therapy. (NCCN 2A)

a. As single agent therapy for distant metastatic disease. (NCCN 2A)

a. Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (≥1%) tumors that are negative for actionable molecular markers* and no contraindications** to PD-1 or PD-L1 inhibitors and ECOG performance status 0-2:

i. In combination with pembrolizumab and carboplatin for squamous cell histology (preferred); (NCCN 1) or

ii. In combination with carboplatin and atezolizumab for nonsquamous cell histology. (NCCN 2A)

*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit.

b. Treatment for recurrent, advanced, or metastatic disease

i. In combination with carboplatin for individuals with ECOG performance status (PS) 0-1 (NCCN 1). (Useful in certain circumstances if contraindications** to PD-1 or PD-L1 inhibitors and PS 0-1 for both nonsquamous cell histology and squamous cell histology, or other recommended regimen for nonsquamous cell histology and PS 2, or preferred for squamous cell histology and PS 2); (NCCN 2A) or

ii. As a single agent for PS 2 (useful in certain circumstances for both nonsquamous cell histology and squamous cell histology). (NCCN 2A)

c. The above regimens are used as:

i. Initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*

ii. First-line (useful in certain circumstances) or subsequent therapy for BRAF V600E-mutation positive tumors

iii. First-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion positive tumors

iv. First-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation positive tumors

v. First-line or subsequent therapy for RET rearrangement positive tumors

vi. Subsequent therapy for EGFR mutation positive (eg, exon 19 deletion or L858R) tumors and prior erlotinib +/- (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib therapy

vii. Subsequent therapy for ALK rearrangement positive tumors and prior crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib therapy

viii. Subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy

ix. Subsequent therapy for PD-L1 expression positive (≥1%) tumors and negative for actionable molecular markers* after prior PD-1/PD-L1 inhibitor but no prior platinum-containing chemotherapy

*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit

d. Treatment for recurrent, advanced, or metastatic disease for individuals with ECOG performance status (PS) 0-1 and no contraindications** to PD-1 or PD-L1 inhibitors, in combination with:

i. Atezolizumab and carboplatin for nonsquamous cell histology; (NCCN 2A) or

ii. Carboplatin and pembrolizumab for squamous cell histology (preferred). (NCCN 1)

e. The above regimens are used as:

i. Initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*

ii. First-line (useful in certain circumstances) or subsequent therapy for BRAF V600E-mutation positive tumors

iii. First-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion positive tumors

iv. First-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation positive tumors

v. Subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy

*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit

f. May be substituted for either paclitaxel or docetaxel in individuals who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for individuals in whom standard hypersensitivity premedications are contraindicated. (NCCN 2A)

g. Single agent (if not already given) as subsequent systemic therapy for recurrent, advanced or metastatic disease in individuals with performance status 0-2.

a. Single-agent therapy for persistent disease or recurrence (NCCN 2A):

i. For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease); or

ii. For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease); or

iii. For complete remission and relapse < 6 months after completing chemotherapy (platinum-resistant disease); or

iv. For radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥ 6 months after completing prior chemotherapy (platinum-sensitive disease).

b. Useful in certain circumstances in combination with carboplatin if platinum-sensitive persistent disease or recurrence for indiviiduals with confirmed taxane hypersensitivity:

i. In individuals with complete remission (NCCN 2A) and relapse ≥ 6 months after completing prior chemotherapy. (First relapse NCCN 1, subsequent relapse NCCN 2A)

c. May be a substitute for paclitaxel in individuals who experience a hypersensitivity reaction to paclitaxel. (NCCN 2A)

a. Preferred neoadjuvant therapy in combination with gemcitabine with or without subsequent chemoradiation for (NCCN 2A):

i. Resectable disease, particularly in high-risk individuals (i.e., very highly elevated CA 19-9, large primary tumors, large regional lymph nodes, excessive weight loss, extreme pain); or

ii. Biopsy positive borderline resectable disease.

b. First-line therapy, or as induction therapy followed by chemoradiation (useful in certain circumstances in selected individuals without systemic metastases) for individuals with locally advanced disease and good performance status (ECOG PS 0-2) in combination with gemcitabine (preferred regimen). (NCCN 2A)

c. Preferred first-line therapy for metastatic disease in individuals with good performance status (ECOG PS 0-2) in combination with gemcitabine (NCCN 1)

d. Subsequent therapy in combination with gemcitabine for locally advanced or metastatic disease for individuals with good performance status (ECOG PS 0-2), and disease progression who were previously treated with fluoropyrimidine-based therapy. (NCCN 2A)

e. If not previously done, therapy with or without chemoradiation in combination with gemcitabine for local recurrence in the pancreatic operative bed after resection in individuals with good performance status (ECOG PS 0-2): if less than 6 months from completion of primary therapy and previously treated with fluoropyrimidine-based therapy, or if ≥ 6 months from completion of primary therapy. (NCCN 2A)

f. Therapy in combination with gemcitabine for recurrent metastatic disease with or without local recurrence after resection in individuals with good performance status (ECOG PS 0-2): if less than 6 months from completion of primary therapy and previously treated with fluoropyrimidine-based therapy, or if ≥ 6 months from completion of primary therapy. (NCCN 2A)

a. Therapy as a single agent or in combination with gemcitabine for advanced or metastatic disease in individuals with prior oxaliplatin exposure in the adjuvant setting or contraindication (NCCN 2A):

i. As initial therapy; or

ii. As subsequent therapy in individuals who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab.

b. Subsequent therapy as a single agent or in combination with gemcitabine for advanced or metastatic disease in individuals who are appropriate or not appropriate for intensive therapy. (NCCN 2A)

a. Subsequent therapy for disease progression in individuals with good performance (ECOG 0-1, with good biliary drainage and adequate nutritional intake) and pancreatobiliary and mixed type if previously treated with fluoropyrimidine-based therapy

i. In combination with gemcitabine

b. Subsequent therapy for disease progression in select individuals (poor performance status (PS) and ECOG PS 2) with pancreatobiliary and mixed type in combination with gemcitabine.  

c. First line therapy in combination with gemcitabine

i. In individuals with good performance status (PS) ECOG 0-1, with goof biliary drainage and adequate nutritional intake.

ii. To be considered in select individuals with poor performance status and ECOG PS 2

c. To be used for pancreatobiliary and mixed type

i. Unresectable localized disease

ii. Stage IV resected ampullary cancer

iii. Metastatic disease at initial presentation

d. Neoadjuvant therapy, with or without subsequent chemoradiation, in combination with i. Gemcitabine

a. Primary treatment as a single agent (NCCN 2A):

i. With sequential external beam radiation therapy (EBRT) and brachytherapy for disease that is not suitable for primary surgery in individuals with suspected or gross cervical involvement; or

ii. May be considered preoperatively for individuals presenting with abdominal/pelvic confined disease that is suitable for primary surgery; or

iii. With sequential EBRT and with or without brachytherapy for locoregional extrauterine disease that is not suitable for primary surgery; or

iv. With EBRT and/or stereotactic body radiation therapy for distant metastases that are suitable for primary surgery.

b. Adjuvant treatment for surgically staged individuals as a single agent with or without EBRT and with or    without vaginal brachytherapy for stage III-IV disease. (NCCN 2A)

c. Single-agent therapy (NCCN 2A):

i. For disseminated metastases; or

ii. With sequential external beam radiation therapy (EBRT) and with or without brachytherapy for locoregional recurrence in individuals with no prior RT to site of recurrence, or previous brachytherapy only; or

iii. After surgical exploration, with sequential EBRT for locoregional recurrence in individuals with disease confined to the vagina or paravaginal soft tissue, or in pelvic, para-aortic or common iliac lymph nodes; or

iv. After surgical exploration, with or without sequential EBRT for locoregional recurrence in individuals with upper abdominal or peritoneal disease; or

v. With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in individuals who have received prior EBRT to site of recurrence.

c. Single-agent therapy (NCCN 2A):

i. For disease that is suitable for primary surgery as additional treatment with or without sequential external beam radiation therapy (EBRT) and with or without vaginal brachytherapy for stage IB-IV disease: or

ii. For disease that is not suitable for primary surgery as primary treatment with or without sequential EBRT and with or without brachytherapy.

1. Invasive Breast Cancer

• As single agent or in combination with carboplatin for recurrent unresectable (local or regional) or stage IV (M1) HER2 negative disease that is (NCCN 2A):
• Hormone receptor-negative; or
• Hormone receptor-positive with visceral crisis or endocrine therapy refractory.
• Therapy in combination with atezolizumab for PD-L1 positive triple negative recurrent unresectable (local or regional) or stage IV (M1) disease:
• As preferred first-line therapy; (NCCN 1) or
• As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used. (NCCN 2A)
• Therapy in combination with atezolizumab for PD-L1 positive triple negative recurrent unresectable (local or regional) or stage IV (M1) disease (NCCN 2A):
• As preferred first-line therapy; or
• As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used.
• Therapy in combination with atezolizumab for PD-L1 positive triple negative recurrent unresectable (local or regional) or stage IV (M1) disease (NCCN 1):
• As preferred first-line therapy; or
• As second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used.
• May be substituted for other taxanes (paclitaxel or docetaxel) in select patients due to medical necessity (ie, hypersensitivity reaction). (NCCN 2A)

• Single agent therapy or in combination with carboplatin (useful in certain circumstances, in select patients with high tumor burden, rapidly progressing disease, and visceral crisis) for patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-negative disease that is (NCCN 2A):
• Hormone receptor-negative;
• Hormone receptor-positive with visceral crisis or endocrine therapy refractory.
• Therapy in combination with atezolizumab for PD-L1 positive triple negative disease in patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease (NCCN 1):
• as preferred first-line therapy; or
• as second and subsequent lines of therapy if PD-L1 inhibitor has not been previously used.
• Third-line therapy and beyond in combination with trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive disease in patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease that is (NCCN 2A):
• hormone receptor-negative
• hormone receptor-positive with or without endocrine therapy
• Third-line therapy and beyond in combination with trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive disease in patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) disease that is (NCCN 1):
• Hormone receptor-negative; or
• hormone receptor-positive with or without endocrine therapy.
• May be substituted for other taxanes (paclitaxel or docetaxel) in select patients due to medical necessity (ie, hypersensitivity reaction) (NCCN 2A)

• Primary treatment for unresectable or metastatic disease in combination with gemcitabine; (NCCN 2A) or
• Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine. (NCCN 2A)

• Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine. (NCCN 2A)

• Primary treatment for unresectable or metastatic disease in combination with gemcitabine (NCCN 2A); or
• Subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease in combination with gemcitabine. (NCCN 2A).

• Subsequent systemic therapy, given alone (no HIV) or with antiretroviral therapy (ART) for people with HIV (PWH), for relapsed/refractory advanced cutaneous, oral, visceral, or nodal disease that has progressed on or not responded to first-line systemic therapy, and progressed on alternate first-line systemic therapy. (NCCN 2A)

• As a single agent or in combination with carboplatin for metastatic or unresectable disease as second-line or subsequent therapy for disease progression or after maximum clinical benefit from BRAF targeted therapy. (NCCN 2A)

As single agent therapy for distant metastatic disease. (NCCN 2A)

• Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (≥1%) tumors that are negative for actionable molecular markers* and no contraindications** to PD-1 or PD-L1 inhibitors and ECOG performance status 0-2:

• In combination with pembrolizumab and carboplatin for squamous cell histology (preferred); (NCCN 1) or
• In combination with carboplatin and atezolizumab for nonsquamous cell histology. (NCCN 2A)

 

*if there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes

 

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit

 

• Treatment for recurrent, advanced, or metastatic disease
• In combination with carboplatin for patients with ECOG performance status (PS) 0-1 (NCCN 1). (Useful in certain circumstances if contraindications** to PD-1 or PD-L1 inhibitors and PS 0-1 for both nonsquamous cell histology and squamous cell histology, or other recommended regimen for nonsquamous cell histology and PS 2, or preferred for squamous cell histology and PS 2); (NCCN 2A) or
• In combination with carboplatin for patients with ECOG performance status (PS) 2 (NCCN 2A). (Useful in certain circumstances if contraindications** to PD-1 or PD-L1 inhibitors and PS 0-1 for both nonsquamous cell histology and squamous cell histology, or other recommended regimen for nonsquamous cell histology and PS 2, or preferred for squamous cell histology and PS 2); (NCCN 2A) or
• As a single agent for PS 2 (useful in certain circumstances for both nonsquamous cell histology and squamous cell histology). (NCCN 2A)

 

The above regimens are used as:

• Initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*
• First-line (useful in certain circumstances) or subsequent therapy for BRAF V600E-mutation positive tumors
• First-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion positive tumors
• First-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation positive tumors
• First-line or subsequent therapy for RET rearrangement positive tumors
• Subsequent therapy for EGFR mutation positive (eg, exon 19 deletion or L858R) tumors and prior erlotinib +/- (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib therapy
• Subsequent therapy for ALK rearrangement positive tumors and prior crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib therapy
• Subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy
• Subsequent therapy for PD-L1 expression positive (≥1%) tumors and negative for actionable molecular markers* after prior PD-1/PD-L1 inhibitor but no prior platinum-containing chemotherapy

 

*if there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes

 

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit

 

• Treatment for recurrent, advanced, or metastatic disease for patients with ECOG performance status (PS) 0-1 and no contraindications** to PD-1 or PD-L1 inhibitors, in combination with:
• Atezolizumab and carboplatin for nonsquamous cell histology; (NCCN 2A) or
• Carboplatin and pembrolizumab for squamous cell histology (preferred). (NCCN 1)

 

The above regimens are used as:

• Initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*
• First-line (useful in certain circumstances) or subsequent therapy for BRAF V600E-mutation positive tumors
• First-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion positive tumors
• First-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation positive tumors
• Subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy

 

*if there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes

 

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit

 

• May be substituted for either paclitaxel or docetaxel in patients who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for patients in whom standard hypersensitivity premedications are contraindicated. (NCCN 2A)

• Single-agent therapy for persistent disease or recurrence (NCCN 2A):
• For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease); or
• For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease); or
• For complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease); or
• For radiographic and/or clinical relapse in patients with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease).
• Useful in certain circumstances in combination with carboplatin if platinum-sensitive persistent disease or recurrence for patients with confirmed taxane hypersensitivity:
• In patients with complete remission (NCCN 2A) and relapse ≥6 months after completing prior chemotherapy. (First relapse NCCN 1, subsequent relapse NCCN 2A)
• Single-agent therapy for persistent disease or recurrence (NCCN 2A:
• For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease); or
• For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease); or
• For complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease); or
• For radiographic and/or clinical relapse in patients with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease). (NCCN 2A)
• Useful in certain circumstances in combination with carboplatin if platinum-sensitive persistent disease or recurrence for patients with confirmed taxane hypersensitivity

• In patients with complete remission (NCCN 2) and relapse ≥6 months after completing prior chemotherapy. (First relapse NCCN 1, subsequent relapse NCCN 2A)

• Preferred neoadjuvant therapy in combination with gemcitabine with or without subsequent chemoradiation for (NCCN 2A):
• Resectable disease, particularly in high-risk patients (i.e., very highly elevated CA 19-9, large primary tumors, large regional lymph nodes, excessive weight loss, extreme pain); or
• Biopsy positive borderline resectable disease.
• First-line therapy, or as induction therapy followed by chemoradiation (useful in certain circumstances in selected patients without systemic metastases) for patients with locally advanced disease and good performance status (ECOG PS 0-2) in combination with gemcitabine (preferred regimen). (NCCN 2A)
• Preferred first-line therapy for metastatic disease in patients with good performance status (ECOG PS 0-2) in combination with gemcitabine. (NCCN 1)
• Subsequent therapy in combination with gemcitabine for locally advanced or metastatic disease for patients with good performance status (ECOG PS 0-2), and disease progression who were previously treated with fluoropyrimidine-based therapy. (NCCN 2A)
• If not previously done, therapy with or without chemoradiation in combination with gemcitabine for local recurrence in the pancreatic operative bed after resection in patients with good performance status (ECOG PS 0-2): if less than 6 months from completion of primary therapy and previously treated with fluoropyrimidine-based therapy, or if ≥ 6 months from completion of primary therapy. (NCCN 2A)
• Therapy in combination with gemcitabine for recurrent metastatic disease with or without local recurrence after resection in patients with good performance status (ECOG PS 0-2): if less than 6 months from completion of primary therapy and previously treated with fluoropyrimidine-based therapy, or if ≥ 6 months from completion of primary therapy. (NCCN 2A)

• Therapy as a single agent or in combination with gemcitabine for advanced or metastatic disease in patients with prior oxaliplatin exposure in the adjuvant setting or contraindication (NCCN 2A):
• As initial therapy; or
• As subsequent therapy in patients who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab.
• Subsequent therapy as a single agent or in combination with gemcitabine for advanced or metastatic disease in patients who are appropriate or not appropriate for intensive therapy. (NCCN 2A)

• Therapy as a single agent or in combination with gemcitabine for advanced or metastatic disease in patients with contraindication to oxaliplatin (NCCN 2A):
• As initial therapy: or
• As subsequent therapy in patients who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab.
• Subsequent therapy as a single agent or in combination with gemcitabine for advanced or metastatic disease in patients who are appropriate or not appropriate for intensive therapy. (NCCN 2A)

• Primary treatment as a single agent (NCCN 2A):
• with sequential external beam radiation therapy (EBRT) and brachytherapy for disease that is not suitable for primary surgery in patients with suspected or gross cervical involvement; or
• may be considered preoperatively for patients presenting with abdominal/pelvic confined disease that is suitable for primary surgery; or
• with sequential EBRT and with or without brachytherapy for locoregional extrauterine disease that is not suitable for primary surgery; or
• with EBRT and/or stereotactic body radiation therapy for distant metastases that are suitable for primary surgery.
• Adjuvant treatment for surgically staged patients as a single agent with or without EBRT and with or without vaginal brachytherapy for stage III-IV disease. (NCCN 2A)
• Single-agent therapy (NCCN 2A):
• For disseminated metastases; or
• With sequential external beam radiation therapy (EBRT) and with or without brachytherapy for locoregional recurrence in patients with no prior RT to site of recurrence, or previous brachytherapy only; or
• After surgical exploration, with sequential EBRT for locoregional recurrence in patients with disease confined to the vagina or paravaginal soft tissue, or in pelvic, para-aortic or common iliac lymph nodes; or
• After surgical exploration, with or without sequential EBRT for locoregional recurrence in patients with upper abdominal or peritoneal disease; or
• With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in patients who have received prior EBRT to site of recurrence.
• Single-agent therapy (NCCN 2A):
• For disease that is suitable for primary surgery as additional treatment with vaginal brachytherapy for stage IA disease (preferred): or
• For disease that is suitable for primary surgery as additional treatment with or without sequential external beam radiation therapy (EBRT) and with or without vaginal brachytherapy for stage IB-IV disease: or
• For disease that is not suitable for primary surgery as primary treatment with or without sequential EBRT and with or without brachytherapy.

• Per FDA label guidelines.

1. Metastatic breast cancer, after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
2. Locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
3. Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.

• Per FDA label guidelines.

1. Metastatic breast cancer, after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
2. Locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
3. Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.

• Per FDA label guidelines.

1. Metastatic breast cancer, after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
2. Locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
3. Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.

1. Bladder Cancer

• Used as a single agent for clinical stage T4b or T2-4a, N1-3 disease, or for recurrence post cystectomy, or for metastatic disease as subsequent systemic therapy as an alternate regimen

2. Bladder Cancer - Primary Carcinoma of the Urethra

• Used as a single agent as subsequent systemic therapy for recurrent or metastatic disease

3. Upper GU Tract Tumors

• Used as a single agent as subsequent systemic therapy for metastatic disease as an alternate regimen

4. Urothelial Carcinoma of the Prostate

• Used as a single agent as subsequent systemic therapy for metastatic disease as an alternate regimen

5. Metastatic Breast cancer

• Therapy in combination with trastuzumab for human epidermal growth factor receptor 2-positive recurrent or metastatic trastuzumab-exposed disease
• with symptomatic visceral disease or visceral crisis
• that is hormone receptor-negative or hormone receptor-positive and endocrine therapy refractory

6. Cervical Cancer

• Second-line therapy as a single agent for either local/regional recurrence or distant metastases

7. Melanoma

• Single-agent therapy for metastatic or unresectable disease as second-line or subsequent therapy for disease progression or after maximum clinical benefit from BRAF targeted therapy for patients with performance status 0-2

8. Non-Small Cell Lung Cancer (NSCLC)

• Treatment for recurrence or metastasis as a single agent for patients with performance status (PS) 2 or in combination with carboplatin for (PS) 0-2 as
• subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, or osimertinib therapy
• subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, or alectinib therapy
• subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib therapy
• subsequent therapy for PD-L1 expression-positive (≥50%) and EGFR, ALK, and ROS1 negative tumors and prior pembrolizumab therapy

9. Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

• Single-agent therapy for persistent disease or recurrence