Medical Policies - Prescription Drugs


Cabazitaxel (Jevtana)

Number:RX502.032

Effective Date:10-01-2018

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, DrugDex (IIb strength of recommendation 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 0 - 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 Prostate-specific antigen (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 >3x upper limit of normal (ULN).

NOTE 1: Authorizations for initial and/or continued use shall be limited to 12 months.

Description:

Prostate cancer is the second leading cause of cancer-related deaths among American men with an estimated 164,690 new cases diagnosed per year. (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 or recurrent prostate cancer following treatment of localized disease. Androgen deprivation therapy (ADT) is the standard treatment for metastatic or recurrent prostate cancer however, some patients eventually develop androgen-independent prostate cancer, also known as metastatic, hormone-refractory prostate cancer (mHRPC). (2) When evaluated patients, oncologists typically utilize the Eastern Cooperative Oncology Group (ECOG) Performance Status (3) to assess disease progression, the impact on an individual’s activities of daily living, and to determine the individual’s treatment plan and general prognosis (see table 1).

Table 1: ECOG Performance Status (3)

Grade

ECOG

0

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

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.

2

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

3

Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours.

4

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. (4) 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 (4):

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 (4):

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 cabazitaxel. Cabazitaxel is contraindicated in patients with neutrophil counts ≤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 cabazitaxel infusion and administration of appropriate therapy. Patients should receive premedication. Cabazitaxel 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 August 12, 2018. Following is a summary of the key literature to date.

Prostate Cancer

In 2010, the 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. (4, 5) 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. (3) 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, Aspartate aminotransferase (AST) <1.5 x ULN, and alanine aminotransferase (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 (hazard ratio [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.) (6):

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. (7) 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.

In 2017, Eisenberger and colleagues (8) noted that cabazitaxel 25 mg/m2 (C25) significantly improved OS versus mitoxantrone (P < .001) in post docetaxel patients with mCRPC in the phase III TROPIC study. The phase III PROSELICA study (NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m2 (C20) versus C25 in postdocetaxel patients with mCRPC. Patients were stratified by ECOG performance status, measurability of disease per RECIST, and region, and randomly assigned to receive C20 or C25. To claim noninferiority of C20 (maintenance of ≥ 50% of the OS benefit of C25 versus mitoxantrone in TROPIC) with 95% confidence level, the upper boundary of the CI of the HR for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary end points included PFS, prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety. Overall, 1,200 patients were randomly assigned (C20, n=598; C25, n=602) and the baseline characteristics were similar in both arms. Median OS was 13.4 months for C20 and 14.5 months for C25 (HR, 1.024). The upper boundary of the HR CI was 1.184 (less than the 1.214 noninferiority margin). Significant differences were observed in favor of C25 for PSA response (C20, 29.5%; C25, 42.9%; nominal P<0.001) and time to PSA progression (median: C20, 5.7 months; C25, 6.8 months; HR for C20 versus C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between cohorts. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. The study confirmed the efficacy of cabazitaxel in post docetaxel patients with mCRPC. The noninferiority end-point was met; C20 maintained ≥50% of the OS benefit of C25 versus mitoxantrone in TROPIC. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.

DynaMed Plus

In 2018, DynaMed Plus (9) published a paper on the management of metastatic CRPC that included the following recommendations:

For second-line salvage treatment for symptomatic metastases, provide best supportive care and consider cabazitaxel plus prednisone in patients with prior docetaxel (NCCN Category 1; EAU Grade A, Level 1a);

Cabazitaxel may improve survival compared to mitoxantrone in patients with metastatic CRPC progressing after docetaxel therapy (level 2 [mid-level] evidence).

Bladder (Urothelial) Cancer

In 2017, Bellmunt et al. (10) completed a multicenter, randomized, open-label, phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN). ECOG Performance Status, anemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and OS for the phase III. Seventy patients were included in the phase II study across 19 institutions in Europe. Baseline characteristics were balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and 6 patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median PFS for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P=0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for OS benefit was found favoring vinflunine (median 7.6 versus 5.5 months). Grade 3 to 4 related adverse events were seen in 41% patients with no difference between the two arms. This study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy in the cabazitaxel arm. Vinflunine results were consistent with those known previously.

Breast Cancer

In a 2017 prospective, multi-center, randomized, open-label, phase II clinical trial, Kummel and colleagues (11) compared the safety and effectiveness of four 3-weekly cycles cabazitaxel versus 12 weeks of paclitaxel given as neoadjuvant treatment. The primary end-point was pathological complete response (pCR) rate defined as the complete absence of invasive carcinoma on histological examination of the breast irrespective of lymph node involvement after the taxane treatment. Patients could receive an anthracycline-based therapy thereafter. A total of 333 patients were randomized and started treatment with 74.7% and 83.2% of patients completing treatment in the cabazitaxel and paclitaxel arms, respectively. Patients in cabazitaxel arm had a significantly lower pCR rate compared to the paclitaxel arm (1.2 % versus 10.8 %; p=0.001). A total of 42 (25.3%) patients in the cabazitaxel arm and 17 (10.2 %) in the paclitaxel arm had at least 1 serious adverse event. Dose reductions were observed in 9.6% patients in the cabazitaxel arm compared to 11.4% in the paclitaxel arm (p=0.721). The main reason for dose reductions was due to non-hematological toxicities in 3.0% versus 7.8% (p=0.087), respectively. The GENEVIEVE study showed no short-term effect of cabazitaxel in triple-negative or luminal B/HER2-negative primary breast cancer, while there seemed to be no differences in drug exposure and patient compliance between the 2 arms.

Head and Neck Cancer

In a 2016 phase II clinical trial, Machiels et al. (12) examined the effects of cabazitaxel in patients with recurrent squamous cell carcinoma of the head and neck. Patients with incurable squamous cell carcinoma of the head and neck with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of non-hematological adverse events greater than grade 2 and hematological adverse events greater than grade 3 or methotrexate (40 mg/m2/week). Patients were stratified according to their ECOG performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary end-point was the PFS rate at 18 weeks. Of the 101 patients, 53 and 48, with a median age of 58.0 years (range of 41 to 80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFS rate at 18 weeks was 13.2% (95 CI: 5 % to 25%) for cabazitaxel and 8.3% (95% CI: 2% to 20%) for methotrexate. The median PFS was 1.9 months in both arms. The median OS was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced SAEs with cabazitaxel than with methotrexate (54% versus 36%). The most common drug-related grade 3 to 4 AE in the cabazitaxel arm was febrile neutropenia (17.3%). The authors concluded that the findings of this study did not meet its primary end-point; cabazitaxel had low activity in recurrent SCCHN and the toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17 %).

In a 2017 multi-center, phase II clinical trial, Fayette et al. (13) examined the effects of cabazitaxel in patients with recurrent/metastatic head and neck squamous cell carcinoma who had previously failed platinum, cetuximab and taxane based chemotherapy. The criteria included progressive patients with an ECOG of less than or equal to 2. Cabazitaxel was given at 25 mg/m²/3 weeks (maximum of 10 cycles), with growth factor support. Efficacy was assessed every 6 weeks. The primary end-point was control rate at 6 weeks. A Simon's 2-stage optimal design (P0=0.10; P1=0.30) required 29 evaluable patients. At the end of the trial, at least 6 non-progressions were needed to consider the drug worthy of additional study. Out of the 31 enrolled patients, 29 were eligible; 42% had received at least 3 previous lines of chemotherapy. For the primary end-point, 8 patients (27.6 %; 95 % CI: 12.7 % to 47.2 %) had stable disease at 6 weeks. Median PFS was 1.05 months (95 % CI: 0.69 to 2.07). All patients were analyzed for toxicity: 6 patients had febrile neutropenia. During the 81 cycles administered, 49 events (grade 3 to 5) were observed in 81% of the patients, including 35 severe adverse events of which 15 were related to cabazitaxel. The authors concluded that although cabazitaxel met its primary end-point to deserve further investigation, its toxicity made it difficult to use in frail patients and new schemes are needed (e.g., 20 mg/m2) if further investigations are initiated.

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, in 2015, Evans et al. investigated the use of cabazitaxel versus topotecan in patients with SCLC with progressive disease during or after first-line platinum-based chemotherapy. (14) 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 PFS compared with topotecan (1.4 versus 3.0 months, respectively; two-sided p<0.0001; HR=2.17, 95% CI=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; HR=1.57, 95% CI=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.

Cabazitaxel was hypothesized to increase objective response rate (ORR) when used as second-line therapy in non-small cell lung cancer (NSCLC). To evaluate this theory, Madan et al. (15) performed a phase II, 2-stage trial in 28 patients using two different treatment schedules (A: 20 mg/m2 every 3 weeks intravenously; B: 8.4 mg/m2 intravenously weekly) to determine the ORR of cabazitaxel with secondary end-points including PFS, safety, and OS. There was one objective response in schedule B. PFS and OS of schedule A was 3 and 6 months, respectively. PFS and OS of schedule B was 3 and 13 months, respectively. The stable disease rate was higher in schedule A (SD = 69.23 %; 95 % CL 38.57, 90.90) compared to schedule B (SD = 38.46 %; 95 % CL 13.86, 68.42), but this difference was not statistically significant (P value = 0.1156). There were two grade 5 toxicities from sepsis. Hematuria developed in a higher percentage of patients (35%) as compared to the prior cabazitaxel phase 3 trial which led to a change in protocol. The authors noted that the response to cabazitaxel in NSCLC was not as robust as seen in prostate cancer and it was not superior to currently used agents such as docetaxel, pemetrexed, and erlotinib. In absence of significant objective responses, the second stage of the study was not undertaken.

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). (16)

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. (17) 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 2018, NCCN updated their guidelines for prostate cancer (2) and included cabazitaxel with concurrent steroid (dexamethasone, 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 should not be used in patients with severe hepatic dysfunction.

NCCN encourages men with mCRPC that has progressed following docetaxel-based chemotherapy to participate in clinical trials. NCCN states cabazitaxel with concurrent steroids (dexamethasone/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.

NCCN does not mention the use of cabazitaxel as a treatment option for the treatment of bladder cancer, breast cancer, head and neck cancer, and lung cancer. (18-22)

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 in 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, adrenocortical carcinoma, 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 4, 2018. Available at <http://www.cancer.org> (accessed August 13, 2018).

2. National Comprehensive Cancer Network (NCCN). The NCCN guidelines for Prostate Cancer.V.3.2018. Available at <http://www.nccn.org> (accessed August 13, 2018).

3. 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

4. US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Product approval information, Cabazitaxel (Jevtana®). June 17, 2010 (revised January 9, 2018). Available at <http://www.fda.gov> (accessed August 13, 2018).

5. Mckee, A and Waxman I. US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Clinical review #20-1023. March 2010. Available at <http://www.accessdata.fda.gov> (accessed August 13, 2018).

6. 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.

7. 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

8. Eisenberger M1, Hardy-Bessard AC1, Kim CS1, et al. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients with Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017 Oct 1; 35(28):3198-3206. PMID 28809610

9. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995. Record No. 906169. Management of castration-resistant metastatic prostate cancer; [updated 2018 Jul 27; Available at <http://www.dynamed.com> (accessed August 13, 2018).

10. Bellmunt J, Kerst JM, Vázquez F, Et al. A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN). Ann Oncol. 2017 Apr 13. PMID 28419193

11. Kümmel S, Paepke S, Huober J, et al. Randomised, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE). Eur J Cancer. 2017 Oct; 84:1-8. PMID 24217332

12. Machiels JP, Van Maanen A, Vandenbulcke JM, et al. Randomized phase II study of cabazitaxel versus methotrexate in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck previously treated with platinum-based therapy. Oncologist. 2016; 21(12):1416-e17. PMID 27903924

13. Fayette J, Guigay J, Le Tourneau C, et al. Cabazitaxel in recurrent/metastatic squamous cell carcinoma of the head and neck: Phase II UNICANCER trial ORL03. Oncotarget. 2017 Mar 4. PMID 28881692

14. 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

15. Madan A, Jones BS, Bordoni R, et al. Phase II study of a novel taxane (Cabazitaxel-XRP 6258) in previously treated advanced non-small cell lung cancer (NSCLC) patients. Cancer Chemother Pharmacol. 2016 Sep; 78(3):509-15. PMID 27417317

16. Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients with Intracranial Metastases (2017 July 2) NCT01934894. In: ClinicalTrials.gov. Bethesda (MD). National Institutes of Health. Available at <https://clinicaltrials.gov> (accessed August 14, 2018).

17. National Institute For Health and Clinical Excellence (NICE). Cabazitaxel for hormone-relapsed metastatic prostate cancer treated with docetaxel. Technology Appraisal Guidance TA391. (August 24, 2016). Available at <https://www.nice.org.uk> (accessed August 15, 2018).

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22. National Comprehensive Cancer Network (NCCN). The NCCN guidelines for Non-Small Cell Lung Cancer.V.5.2018. Available at <http://www.nccn.org> (accessed August 15, 2018).

Policy History:

Date Reason
10/1/2018 Document updated with literature review. Added note to Coverage: Authorizations for initial and/or continued use shall be limited to 12 months. Added references 8-13, 15, 18-22.
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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