Prior Auth Protocol

FDA Approved Indications:

For the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of metastatic colorectal cancer

AND

Failure or clinically significant adverse effects to fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy (e.g., FOLFOX, FOLFIRI) and an anti-VEGF therapy (e.g., Avastin^R, Zaltrap^R)

AND

If tumor expresses the KRAS wild type gene, failure or clinically significant adverse effects to an anti-EGFR therapy (e.g., Erbitux^R, Vectibix^R)

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Avastin and Zaltrap are anti-VEGF therapies approved for colorectal cancer.
Erbitux and Vectibix are anti-EGFR therapies approved for colorectal cancer.
Tumors that have a mutation in the codon 12 or codon 13 of the KRAS gene are essentially insensitive to EGFR inhibitors such as Erbitux or Vectibix. Patients with this mutation should not be treated with EGFR inhibitors either alone or in combination with other anticancer agents, as there is virtually no chance of benefit and unnecessary exposure to increased toxicity.
5-fluorouracil (5-FU) and Xeloda are examples of fluoropyrimidine chemotherapeutic agents.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Avastin* (bevacizumab)	5 or 10 mg/kg IV every 14 days in combination with 5-FU based chemotherapy	20 mg/kg
Irinotecan* (Camptosar^R)	125 mg/m² IV in combination with 5-FU based chemotherapy	350 mg/m²
Oxaliplatin (Eloxatin^R)	85 mg/m² IV in combination with 5-FU based chemotherapy	130 mg/m²
Erbitux* (cetuximab)	400 mg/m² IV for initial dose, then weekly infusions of 250 mg/m² IV	400 mg/m²
Cyramza* (ramucirumab)	8 mg/kg IV every 2 weeks plus FOLFIRI regimen	10 mg/kg per dose
5 FU (fluorouracil)	400 mg/m²IV on day 1, 1200 mg/m² for 2 days	2400 mg/m²
Vectibix* (panitumumab)	6 mg/kg IV every 2 weeks	9 mg/kg every 3 weeks
Zaltrap* (ziv-aflibercept)	4 mg/kg IV every 2 weeks plus FOLFIRI regimen (irinotecan, leucovirn, 5-FU)	4 mg/kg
FOLFOX = Infusional 5-FU/leucovorin(LV) /Eloxatin^TM (oxaliplatin)	Eloxatin (oxaliplatin) 85 mg/m² IV over 2 hours day 1; leucovorin 200 mg/m²IV over 2 hours day 1 & 2, followed by 5-FU 400 mg/m² IV bolus over 2-4 minutes, followed by 600 mg/m² IV 5-FU continuous infusion over 22 hours on day 1 & 2. Repeat cycle every 14 days	Varies upon protocol and patient tolerance
FOLFIRI = Infusional 5-FU/leucovorin/Camptosar (irinotecan)	Camptosar (irinotecan) 180 mg/m² IV over 90 minutes day 1; Leucovorin 400 mg/m² IV over 2 hours day 1 followed by 5-FU 400 mg/m² IV bolus over 2-4 minutes, followed by 2.4-3 gm/m² IV 5-FU continuous infusion over 46 hours. Repeat cycle every 14 days	Varies upon protocol and patient tolerance
Stivarga^R (regorafenib)	160 mg PO QD for the first 21 days of each 28-day cycle	160 mg/day
Xeloda^R(capecitabine)	1,250 mg/m² PO bid days 1-14. Repeat every 21 days for 8 cycles.	Varies upon protocol and patient tolerance

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Lonsurf (trifluridine and tipiracil)	Metastatic Colorectal Cancer 35 mg/m²/dose dosed PO BID on days 1 through 5 and Days 8 through 12 of each 28-day cycle.	Length of Benefit

Product Availability:

Tablet:

15 mg trifluridine/6.14 mg tipiracil

20 mg trifluridine /8.19 mg tipiracil

References:

1. Lonsurf [Prescribing Information]. Princeton, NJ: Tahio Oncology; 2015.

2. Mayer RF, Cutsem EV, Falcone A, et al.; Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer. N Engl J Med. 2015; 372:1909-1919

3. National Cancer Institute; Surveillance, Epidemiology, and End results Program Fact Sheet: Colon and Rectum. http://seer.cancer.gov/statfacts/html/colorect.html. Accessed October 2015.

4. Thomson MICROMEDEX, Thomson Healthcare, Inc. http://www.micromedex.com/ . Accessed October 2015.