Pending Policies - Prescription Drugs


Cabazitaxel (Jevtana)

Number:RX502.032

Effective Date:12-01-2017

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Medical policies are a set of written guidelines that support current standards of practice. They are based on current peer-reviewed scientific literature. A requested therapy must be proven effective for the relevant diagnosis or procedure. For drug therapy, the proposed dose, frequency and duration of therapy must be consistent with recommendations in at least one authoritative source. This medical policy is supported by FDA-approved labeling and nationally recognized authoritative references. These references include, but are not limited to: MCG care guidelines, Hayes, DrugDex (IIb level of evidence or higher), NCCN Guidelines (IIb level of evidence or higher), NCCN Compendia (IIb level of evidence or higher), professional society guidelines, and CMS coverage policy.

When the requested chemotherapeutic agent is being utilized in a regimen in combination with other chemotherapeutic agents, the entire regimen (including dose, frequency, and duration) must be consistent with recommendations in at least one authoritative source, including but not limited to FDA labeling and nationally recognized compendia or clinical guidelines such as National Comprehensive Cancer Network (NCCN) and CMS coverage policy. HCSC may require a provider submit documentation from nationally recognized compendia, clinical guidelines, or active Phase III clinical trials supporting the requested regimen.

Cabazitaxel (Jevtana®) in combination with prednisone may be considered medically necessary for the treatment of adult patients (18 years of age or older) with hormone-refractory metastatic prostate cancer when ALL the following criteria are met:

The individual was previously treated with a docetaxel-containing treatment regimen; AND

The individual’s neutrophils are >1,500/mm3; AND

The individuals Eastern Cooperative Oncology Group (ECOG) performance status is 0-2, defined as:

o A - Fully active, able to carry on all pre-disease performance without restriction,

o 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, (e.g., light house work, office work),

o 2 - Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours.

Continued use of cabazitaxel (Jevtana®) is considered not medically necessary for hormone-refractory metastatic prostate cancer when:

The individual has developed intolerance to cabazitaxel (Jevtana®); OR

The individual’s neutrophils are <1,500/mm3; OR

The disease has progressed despite the use of cabazitaxel (Jevtana®); progression is defined as ONE of the following:

o Progressive measurable disease, evidenced by changes in size of lymph nodes or parenchymal masses on physical examination or radiographic studies; OR

o Bone scan progression, evidenced by 1 or more new lesions or increase in size of lesions (not including "flare" that occurs at commencement of hormonal therapy or chemotherapy); OR

o PSA progression, evidenced by an increase in PSA over a previous reference value, where the PSA value is measured a minimum of 1 week from the reference value, and the PSA measurement is a minimum of 25 % greater than the reference value, or an absolute-value increase in PSA of at least 5 ng/ml over the reference value, and the PSA increase is confirmed with repeat testing.

Cabazitaxel (Jevtana®) is considered experimental, investigational and/or unproven for all other indications including but not limited to, severe hepatic impairment defined as total bilirubin >3 x upper limit of normal (ULN).

Description:

Prostate cancer is the third leading cause of cancer-related deaths among American men with an estimated 161,360 new cases diagnosed per year. An estimated number of 26,730 deaths are anticipated in 2017. (1) Prostate cancer is typically diagnosed at a localized stage, and is treated with prostatectomy or radiation therapy however, some patients are diagnosed with metastatic disease or recurrent disease after treatment of localized disease. Androgen deprivation therapy (ADT) is the standard treatment for metastatic or recurrent disease. However, some patients eventually develop androgen-independent prostate cancer (metastatic, hormone-refractory prostate cancer [mHRPC]). (2) At this stage of metastatic disease, the first line chemotherapeutic agent docetaxel has been demonstrated to have a median survival benefit of 18.9 months in randomized clinical trials. (3) Occasionally, Docetaxel therapy may fail due to progressive disease or toxicity. Typically, oncologists utilize the Eastern Cooperative Oncology Group (ECOG) Performance Status (4) to assess disease progression, impact on an individual’s activities of daily living, and to determine an individual’s treatment plan and general prognosis (see table 1).

Table 1: ECOG Performance Status

Grade

ECOG

1

Fully active, able to carry on all pre-disease performance without restriction.

2

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

3

Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours.

4

Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

5

Dead.

Regulatory Status

On June 17, 2010, the U.S. Food and Drug Administration (FDA) approved cabazitaxel (Jevtana) for use in combination with prednisone for treatment of patients with mHRPC previously treated with a docetaxel-containing regimen. (5) Like docetaxel, cabazitaxel is part of a class of drugs known as taxanes. Cabazitaxel, a microtubule inhibitor, was designed to be active in cells that develop resistance to docetaxel. Cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions. The drug appears to elude a mechanism in prostate cancer cells that pumps anticancer drugs out of the cells before they have a chance to be effective. (5)

The current prescribing information for cabazitaxel (Jevtana) includes the following contraindications and Black Box Warnings (5):

Contraindications:

Jevtana is contraindicated in individuals with:

• Neutrophil counts of ≤ 1,500/mm3;

• History of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80;

• Severe hepatic impairment (total bilirubin > 3 x upper limit of normal).

Black Box Warnings:

• Neutropenia: Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia, frequent blood cell counts should be performed on all patients receiving Jevtana. Jevtana is contraindicated in patients with neutrophil counts of ≤1,500 cells/mm3.

• Severe hypersensitivity: Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of the Jevtana infusion and administration of appropriate therapy. Patients should receive premedication. Jevtana is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80.

Rationale:

This policy was originally developed in 2012 and has been updated with searches of scientific literature through May 28, 2017. Following is a summary of the key literature to date.

Prostate Cancer

In 2010, the United States (U.S.) Food and Drug Administration (FDA) approval of cabazitaxel (Jevtana®) was based primarily on the results of a randomized, open-label, international trial of 755 patients from 146 sites in 26 countries. (5, 6) The study spanned from January 2, 2007 to September 25, 2009 and included patients over 18 years of age (range 49-62) with metastatic hormone-refractory prostate cancer (mHRPC) either measurable by RECIST (Response Evaluation Criteria in Solid Tumors) criteria or non-measurable disease with rising prostate-specific antigen (PSA) levels or appearance of new lesions, and ECOG (Eastern Cooperative Oncology Group) performance status of 0-2. Patients were required to have neutrophils >1,500 cells/mm3, platelets > 100,000 cells/mm3, hemoglobin > 10 g/dL, creatinine < 1.5 x upper limit of normal (ULN), total bilirubin < 1 x ULN, AST < 1.5 x ULN, and ALT < 1.5 x ULN. Patients with a history of congestive heart failure or myocardial infarction within the last six months, or patients with uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension were excluded from the study. Patients were randomized to receive either cabazitaxel 25 mg/m2 intravenously every three weeks in combination with prednisone 10 mg/day, or mitoxantrone 12 mg/m2 intravenously every three weeks in combination with prednisone 10 mg/day. Patients were treated until disease progression, death, unacceptable toxicity, or completion of 10 cycles of therapy. Median survival was 15.1 and 12.7 months for cabazitaxel treated and mitoxantrone treated patients, respectively [HR 0.70 (95% CI 0.59-0.83), p<0.0001.] Response rates using RECIST criteria was 14.4 and 4.4% for cabazitaxel treated and mitoxantrone treated patients, respectively, p=0.0005. No complete responses were observed on either arm. The most common (≥10%) grade 1-4 adverse reactions included neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia and alopecia. The most common (≥5%) grade 3-4 adverse reactions were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue and asthenia. Deaths due to causes other than disease progression within 30 days of the last dose were reported in 18 (5%) cabazitaxel-treated patients and 3 (<1%) mitoxantrone-treated patients. The most common fatal adverse reactions in cabazitaxel-treated patients were infections (n=5), and renal failure (n=4). One death was due to diarrhea-induced dehydration and electrolyte imbalance. Due to the risk of severe hypersensitivity, patients should be premedicated with an antihistamine, a corticosteroid and a histamine 2 (H2) antagonists. In addition, antiemetic prophylaxis is recommended. The significant adverse event of neutropenia present in this study suggests that individuals treated with cabazitaxel require an adequate neutrophil count prior to the start of therapy.

Disease progression is defined by the following parameters (Bubly et al.) (7):

1. Progressive measurable disease, evidenced by changes in size of lymph nodes or parenchymal masses on physical examination or radiographic studies; or

2. Bone scan progression, evidenced by 1 or more new lesions or increase in size of lesions (not including "flare" that occurs at commencement of hormonal therapy or chemotherapy); or

3. PSA progression, evidenced by an increase in PSA over a previous reference value, where the PSA value is a measured a minimum of 1 week from the reference value, and the PSA measurement is a minimum of 25 % greater than the reference value, and an absolute-value increase in PSA of at least 5 ng/ml over the reference value, and this PSA increase is confirmed by a second value

In 2015, Lorente D. et al. (8) evaluated how baseline neutrophil-lymphocyte ratio (NLR) was associated with survival and response to treatment in second-line chemotherapy for advanced prostate cancer independent of baseline steroid use. Since NLR is proposed as an indicator of cancer-related inflammation and has known prognostic value in prostate cancer, this study examined its association with overall survival (OS) and response in patients treated with second-line chemotherapy. Patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the TROPIC trial were assessed. Cox regression models were used to investigate the association of baseline NLR (BLNLR) with OS and the significance of a change in NLR count with treatment. Logistic regression models were used to determine the association of BLNLR counts with PSA and RECIST responses. The optimal NLR cut-off was established based on the concordance index of different values. Data from 755, 654 and 405 patients was available for OS, PSA and RECIST response analysis. Median OS was 14.0 months [95% confidence interval (CI) 13.2-14.8]. Median NLR was 2.9. BLNLR was associated with survival (HR 1.5, 95% CI 1.1-2.1, P = 0.011) in multivariable analysis (MVA) independently of variables included in the Halabi nomogram, treatment arm and corticosteroid use. The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival. BLNLR ≥3.0 was associated with lower PSA response (40.1% versus 59.9%; P < 0.001) and RECIST response (7.7% versus 15.6%, P = 0.022) in MVA. Conversion from high (≥3) to low (<3) NLR was associated with improved survival (HR 0.66; 95% CI 0.51-0.85; P = 0.001) and higher PSA response rates (66.4% versus 33.6%; P = 0.000). Use of corticosteroids at baseline did not modify the association between NLR and survival. The authors concluded that NLR is a valid prognostic biomarker in castration-resistant prostate cancer (CRPC) and is associated with survival, PSA and RECIST responses in patients treated with second-line chemotherapy. Changes in NLR counts with treatment may indicate benefit. NLR prognostic value is independent of prior use of corticosteroids.

Lung Cancer

Patients with small-cell lung cancer (SCLC) typically respond well to initial chemotherapy. However, relapse invariably occurs, and topotecan, the only approved second-line treatment option, has limited efficacy. Therefore, Evans et al. (2015) investigated the use of cabazitaxel versus topotecan in patients with SCLC with progressive disease during or after first-line platinum-based chemotherapy. (9) Patients with SCLC who relapsed after initial platinum-based chemotherapy were randomly assigned to receive cabazitaxel 25 mg/m every 21 days or topotecan 1.5 mg/m on days 1-5 every 21 days. Two patient subgroups, defined by chemosensitive and chemo-resistant/refractory disease, were assessed in combination and separately. The safety of cabazitaxel and topotecan was consistent with previous studies, and despite considerable toxicity in both arms, no new safety concerns were identified. Patients that received cabazitaxel had inferior progression-free survival (PFS) compared with topotecan (1.4 versus 3.0 months, respectively; two-sided p < 0.0001; hazard ratio = 2.17, 95% confidence interval = 1.563-3.010), and results were similar in both the chemosensitive and chemorefractory subgroups. No complete responses were observed in either arm, and no partial responses were observed in the cabazitaxel group. The partial response rate in the topotecan arm was 10%. Median OS was 5.2 months in the cabazitaxel arm and 6.8 months in the topotecan arm (two-sided p = 0.0125; hazard ratio = 1.57, 95% confidence interval = 1.10-2.25). cabazitaxel was noted to have inferior efficacy when compared with standard-dose topotecan in the treatment of relapsed SCLC. Topotecan remains a suboptimal therapy, and continued efforts to develop improved second-line treatments are warranted.

Ongoing and Unpublished Clinical Trials

Multiple clinical trials are in progress to evaluate the use of cabazitaxel (Jevtana) for the treatment of other cancers, including but not limited to, ovarian cancer, breast cancer, urothelium transitional cell carcinoma, brain and testicular cancer. One study for the use of cabazitaxel (Jevtana) in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer with intracranial metastases was terminated prematurely due to the lack of efficacy (NCT01934894). (10)

Professional Guidelines and Position Statements

National Institute for Health and Clinical Excellence (NICE)

In 2016, NICE published guidance on the use of cabazitaxel for hormone relapsed prostate cancer treated with docetaxel. (11) The guidance supports cabazitaxel in combination with prednisone as an option for treating mHRPC in individuals whose disease has progressed during or after docetaxel chemotherapy only if treatment with cabazitaxel is stopped when the disease progresses.

National Comprehensive Cancer Network (NCCN)

In February 2017, NCCN updated their guidelines for prostate cancer. (2) NCCN included cabazitaxel with prednisone as an option for second line therapy after docetaxel failure in patients with symptomatic mCRPC. This is a category 1 recommendation based on data from a randomized phase 3 study. NCCN advises physicians to follow current guidelines for prophylactic white blood cell growth factor use; to provide supportive care, including antiemetics and symptom-directed anti-diarrheal agents; and to stop cabazitaxel upon clinical disease progression or intolerance. In addition, cabazitaxel has not been tested in patients with hepatic dysfunction and should not be used on these patients. Cabazitaxel should be stopped upon clinical disease progression or intolerance.

The NCCN guideline encourages men with mCRPC that has progressed following docetaxel based chemotherapy to participate in clinical trials. NCCN states cabazitaxel with prednisone has been shown to prolong overall survival, progression free survival, and PSA and radiologic responses when compared with mitoxatrone and prednisone and is FDA approved in the post docetaxel second line setting. Selection of patients without severe neuropathy and adequate liver, kidney and bone marrow function is necessary, given the risk for neutropenia and other side effects in this population. It is recommended that patients are closely monitored with radiological imaging (i.e. bone scan, CT scan), PSA tests and clinical exams for evidence of progression. Therapy should be continued until clinical progression or intolerability in cases were PSA or bone scan changes may indicate flare rather than true clinical progression. Rising PSA should not be used as a sole criterion for disease progression. Assessment of response should incorporate clinical and radiographic criteria.

Summary of Evidence

Cabazitaxel (Jevtana®) in combination with prednisone may be considered medically necessary for the treatment of adult patients with metastatic hormone-refractory prostate cancer (mHRPC). The FDA approval is supported by a study which includes criteria which the individual was previously treated with a docetaxel-containing treatment regimen, the neutrophils were >1,500/mm3; and the Eastern Cooperative Oncology Group (ECOG) performance status was between 0-2.

Multiple clinical trials are in progress to evaluate the use of cabazitaxel (Jevtana) for the treatment of solid tumors, including but not limited to, ovarian cancer, breast cancer, urothelium transitional cell carcinoma, brain and testicular cancer. Current evidence of published literature is insufficient to permit scientific conclusions regarding the safety and efficacy for the use of cabazitaxel (Jevtana) for any use other than the FDA-approved indication. Additional randomized controlled trials with sufficiently large sample sizes are needed to identify the safety and efficacy for the use of cabazitaxel outside of the FDA labeled indication.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

N/A

HCPCS Codes

J3490, J9043, J9999

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. What are the key statistics about prostate cancer? Prostate Cancer. American Cancer Society January 5, 2017. Available at <http://www.cancer.org> (accessed June 27, 2017).

2. National Comprehensive Cancer Network (NCCN). The NCCN guidelines for Prostate Cancer.V.2.2017. Available at <http://www.nccn.org> (accessed June 16, 2017).

3. US Food and Drug Administration (FDA), Docetaxel Drug Approval package label. Available at <http://www.accessdata.fda.gov> (accessed June 27, 2017).

4. Oken MM, Creech RH, Tormey DC, et al. Toxicity and Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5:649-655. PMID 7165009

5. US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Product approval information, Cabazitaxel (Jevtana®) June 17, 2010 (revised June 2015). Available at <http://www.fda.gov> (accessed July 28, 2017).

6. McKee A, Waxman, I. US Food and Drug Administration (FDA), Center for Drug Evaluation and Research, Clinical review #201023. March 2010. Available at <http://www.accessdata.fda.gov> (accessed June 28, 2017).

7. Bubley GJ, Carducci M, Dahut W, et al. Eligibility and response guidelines for phase II clinical trials in androgen independent prostate cancer: Recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999; 17:3461-3467.

8. Lorente D, Mateo J, Templeton AJ, et al. Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use. Ann Oncol. 2015 Apr; 26(4):750-5. PMID: 25538172

9. Evans TL, Cho BC, Udud K, et al. Cabazitaxel Versus Topotecan in Patients with Small-Cell Lung Cancer with Progressive Disease During or After First-Line Platinum-Based Chemotherapy. J Thorac Oncol. 2015 Aug; 10(8):1221-8. PMID:26200278

10. Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases (May 2017) NCT01934894. In: ClinicalTrials.gov. Bethesda (MD): National Institutes of Health. Available at <https://clinicaltrials.gov> (accessed June 29, 2017).

11. National Institute For Health and Clinical Excellence (NICE). Cabazitaxel for hormone-relapsed metastatic prostate cancer treated with docetaxel. Technology Appraisal Guidance ta391. (May 25, 2016). Available at <https://www.nice.org.uk> (accessed June 26, 2017).

Policy History:

Date Reason
12/1/2017 Document updated with literature review. The following changes were made to Coverage: (1) Expanded the medically necessary criteria for the use of Cabazitaxel (Jevtana®) in combination with prednisone in patients with hormone-refractory metastatic prostate cancer (2) Added indications when the continued use of cabazitaxel (Jevtana®) is not medically necessary (3) Added an experimental, investigational and/or unproven statement for all other indications including but not limited to, severe hepatic impairment defined as total bilirubin >3 x upper limit of normal (ULN).
9/1/2016 Document updated with literature review. Coverage criteria updated based on labeled indication. 1) Cabazitaxel (Jevtana®) in combination with prednisone may be considered medically necessary for the treatment of adult patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen 2) Cabazitaxel (Jevtana®) is considered experimental, investigational and/or unproven for all other indications.
8/15/2015 Reviewed. No changes.
12/1/2014 Document updated with literature review. Coverage unchanged. FDA Black Box Warning information was moved from Coverage section to Description section.
1/1/2012 New medical document. Cabazitaxel (Jevtana®) may be considered medically necessary for treatment of prostate cancer when stated criteria are met.

Archived Document(s):

Title:Effective Date:End Date:
Cabazitaxel (Jevtana)12-01-201709-30-2018
Cabazitaxel (Jevtana)09-01-201611-30-2017
Cabazitaxel (Jevtana)08-15-201508-31-2016
Cabazitaxel (Jevtana)12-01-201408-14-2015
Cabazitaxel (Jevtana)01-01-201211-30-2014
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