Clinical UM Guideline

 

Subject: Cabazitaxel (Jevtana®)
Guideline #: CG-DRUG-80 Publish Date:    12/12/2018
Status: Reviewed Last Review Date:    11/08/2018

Description

This document addresses cabazitaxel (Jevtana). Cabazitaxel is a tubulin-binding taxane used in combination with prednisone for the treatment of hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen. It acts to inhibit cell division and growth of cancer and can promote cell death. 

Clinical Indications

Medically Necessary:

Cabazitaxel is considered medically necessary for the treatment of hormone-refractory metastatic prostate cancer (also known as castrate-resistant prostate cancer) when all of the following criteria are met:

  1. Cabazitaxel is used in combination with prednisone; and
  2. Disease has progressed during or after treatment with a docetaxel-containing regimen; and
  3. Individual’s current Eastern Cooperative Oncology Group (ECOG) performance status is 0-2.

Not Medically Necessary:

Cabazitaxel is considered not medically necessary when the medically necessary criteria are not met and for the treatment of all other solid tumors and uses, including but not limited to: appendiceal cancer, bladder cancer, brain tumor, breast cancer, head and neck cancer, lung cancer, melanoma and pancreatic cancer.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

 

J9043

Injection, cabazitaxel, 1 mg [Jevtana]

 

 

 

 

ICD-10 Diagnosis

 

C61

Malignant neoplasm of prostate

Z19.2

Hormone resistant malignancy status

Z85.46

Personal history of malignant neoplasm of prostate

Discussion/General Information

In 2018, the American Cancer Society estimates that there will be about 164, 690 new cases of prostate cancer diagnosed in the United States and approximately 29,430 deaths from the disease. The majority (92%) of men with prostate cancer are diagnosed with localized disease for which treatment options are radiotherapy and surgery (Oudard, 2011).

In June 2010, the U.S. Food and Drug Administration (FDA) approved cabazitaxel (Jevtana) in combination with prednisone for the treatment of advanced, hormone-refractory, prostate cancer that has worsened during or after treatment with docetaxel. The FDA-approved agent cabazitaxel has demonstrated an improved rate of survival for men with metastatic castration-resistant prostate cancer progressing during or after treatment with docetaxel.

The safety and efficacy of cabazitaxel plus prednisone for the treatment of prostate cancer was evaluated by de Bono and colleagues (2010) in an open-label randomized phase III trial of men with metastatic castration-resistant prostate cancer who had received previous hormone therapy, but whose disease had progressed during or after treatment with a docetaxel-containing regimen (TROPIC Trial, NCT00417079). The study was undertaken internationally in 26 countries at 146 centers. Inclusion criteria included an age of at least 18 years and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Additional inclusion criteria were previous and ongoing castration by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists, or both; antiandrogen withdrawal followed by progression had to have taken place at least 4 weeks (6 weeks for bicalutamide) prior to enrollment; adequate hematological, hepatic, renal, and cardiac function; and left-ventricular ejection fraction of greater than 50%. Between January 2007 and October 2008, a total of 755 men were treated with 10 mg oral prednisone daily, and randomized to receive either 12 mg/m2 mitoxantrone intravenously over 15-30 minutes (n=377) or 25 mg/m2 cabazitaxel intravenously over 1 hour every 3 weeks (n=378). The random allocation schedule was computer-generated and participants and treating physicians were not masked to treatment allocation; however, the study team was masked to data analysis. The primary endpoint was overall survival and secondary endpoints included progression-free survival and safety. Disease characteristics and demographics of the treatment groups were balanced at baseline. Treatment was continued for a maximum of 10 cycles. Median overall survival was 15.1 months (95% confidence interval [CI], 14.1-16.3) in the cabazitaxel group and 12.7 months (11.6-13.7) in the mitoxantrone group. Median progression-free survival was 2.8 months (95% CI, 2.4-3.0) in the cabazitaxel group and 1.4 months (1.4-1.7) in the mitoxantrone group. Those treated with cabazitaxel had significantly higher tumor and prostate specific antigen (PSA) responses than those treated with mitoxantrone. The most common clinically significant grade 3 or higher adverse events were neutropenia (cabazitaxel, 303 [82%] subjects vs. mitoxantrone, 215 [58%]) and diarrhea (23 [6%] vs. 1 [< 1%]). A total of 28 (8%) men in the cabazitaxel group and 5 (1%) in the mitoxantrone group had febrile neutropenia. 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.

In a 2013 update of the TROPIC trial, Bahl and colleagues demonstrated a sustained survival benefit of cabazitaxel in a subset of individuals who survived 2 years or more with a median follow-up of 25.5 months. Individual characteristics were well balanced within and between those who survived ≥ 2 years and < 2 years. Sixty (15.9%) of 378 subjects in the cabazitaxel group and 31 (8.2%) of 377 subjects in the mitoxantrone group survived ≥ 2 years (odds ratio [OR] 2.11; 95% CI, 1.33-3.33). No statistically significant difference was noted between groups for time to pain progression or pain response.

Eisenberger and colleagues (2017) assessed the noninferiority of cabazitaxel 20 mg/m2 (C20) versus cabazitaxel 25 mg/2 (C25) in the phase III PROSELICA study of postdocetaxel-treated subjects with metastatic castration-resistant prostate cancer. A total of 1200 subjects were randomly assigned to one of two cabazitaxel dose regimens (C20, n=598; C25, n=602). Baseline characteristics were similar in both arms. The median overall survival was 13.4 months and 14.5 months in the C20 and C25 groups, respectively (hazard ratio [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 the C25 group 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 vs. C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between the groups. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. Eight subjects in the C20 group and 15 subjects in the C25 group died from infection; of these, 4 deaths in 580 (0.7%) subjects and 8 deaths in 595 (1.3%) subjects occurred within the first 30 days of treatment in the C20 and C25 groups, respectively. All of the deaths occurred in subjects greater than 60 years of age. The authors concluded the noninferiority endpoint was met, as the C20 group maintained ≥ 50% of the overall survival benefit of C25 versus mitoxantrone as in the TROPIC trial.

In a randomized phase III trial (FIRSTANA; NCT01308567), Oudard and colleagues (2017) evaluated overall survival rates comparing C20 or C25 dose regimens plus daily prednisone to docetaxel as first-line therapy in individuals with metastatic castration-resistant prostate cancer. A total of 1168 chemotherapy-naïve subjects with an ECOG performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or docetaxel (D75) intravenously every 3 weeks plus daily prednisone. Baseline characteristics were similar across cohorts. Secondary endpoints included safety, progression-free survival, tumor, prostate-specific antigen, and pain response, pharmacokinetics, and health-related quality of life. The median overall survival was 24.5, 25.2, and 24.3 months in the C20, C25, and D75 cohorts, respectively. The HR for C20 compared to D75 was 1.01 (95% CI, 0.85 to 1.20; p=0.997), and HR for C25 compared to D75 was 0.97 (95% CI, 0.82 to 1.16; p=0.757). The median progression-free survival was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) compared to D75 (30.9%; nominal p=0.037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. The authors concluded that C20 and C25 treatment regimens did not demonstrate superiority for overall survival compared to subjects in the D75 cohort with chemotherapy-naïve metastatic castration-resistant prostate cancer. Tumor response was numerically higher in the C25 cohort compared to the D75 cohort; however, performance free survival was numerically improved with D75 compared to C25. Overall, less toxicity was reported in the C20 cohort.

Beer and colleagues (2017) evaluated the efficacy and safety of custirsen in combination with cabazitaxel and prednisone compared to cabazitaxel and prednisone alone in a randomised, open-label, international, phase III trial (AFFINITY) of 635 individuals with metastatic castration-resistant prostate cancer previously treated with docetaxel. The trial did not meet the primary endpoint of demonstrating a statistically significant improvement in overall survival for individuals treated with custirsen in combination with cabazitaxel/prednisone compared to cabazitaxel/prednisone alone (median overall survival: 14.1 months [95% CI, 12.7-15.9] in the custirsen group vs. 13.4 months [95% CI, 12.1-14.9] in the control group; HR, 0.95 [95% CI, 0.80-1.12]; log-rank, p=0.53).

The FDA label for cabazitaxel (Jevtana, 2018) includes updated dosing recommendations based on body surface area. A dose of 20 mg/m2 is administered as an intravenous infusion every 3 weeks in combination with oral prednisone (10 mg) administered daily throughout cabazitaxel treatment. A dose of 25 mg/m2 can be used in select individuals at the discretion of the treating provider. Recommendations for dosage modifications (dose reduction) for adverse reactions and an expanded black box warning for monitoring of neutropenia adverse events were added to the FDA label. Additionally, the black box warning recommends primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) in individuals with high-risk clinical features (such as, older individuals, those with poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities) that predispose them to increased complications from prolonged neutropenia; however, the effectiveness of primary prophylaxis with G-CSF has not been studied in individuals receiving cabazitaxel. Thus, the FDA label concludes “therapeutic use of G-CSF and secondary prophylaxis should be considered in all patients at increased risk for neutropenia complications.”

The National Comprehensive Cancer Network® (NCCN) Guidelines for Prostate Cancer (V4.2018) and the NCCN drug compendium currently assign a category 1 recommendation to cabazitaxel with concurrent steroid as subsequent therapy for metastatic castration-recurrent prostate cancer previously treated with a docetaxel-based regimen (if cabazitaxel not previously received).

The American Urological Association (AUA) Clinical Practice Guideline for castration-resistant prostate cancer (2018) includes the following recommendation:

Clinicians should offer treatment with abiraterone + prednisone, cabazitaxel or enzalutamide to patients with mCRPC with good performance status who received prior docetaxel chemotherapy. If the patient received abiraterone + prednisone prior to docetaxel chemotherapy, they should be offered cabazitaxel or enzalutamide. [Standard; Evidence Level Grade A (abiraterone) / B (cabazitaxel)/ A (enzalutamide)].

Other Uses

Cabazitaxel has also been evaluated as a treatment for other indications, including advanced gastric cancer (Kang, 2015), brain tumors (Ghoochani, 2016; Girard, 2015), breast cancer (Kummel, 2017; Villanueva, 2011), small cell lung cancer (Evans, 2015) and other solid malignancies (appendiceal, melanoma, lung, pancreas, bladder, and head and neck cancer) (Joshi, 2017; Rixe, 2015). In a randomized phase II/III study of comparing cabazitaxel to vinflunine in individuals with metastatic or locally advanced transitional cell carcinoma of the urothelium, cabazitaxel showed a lack of efficacy as second-line therapy in the treatment of bladder cancer (Bellmunt, 2017). The current peer-reviewed published literature does not support that the use of cabazitaxel to treat these conditions provides additional benefit compared to other chemotherapy regimens. The FDA has not approved use of cabazitaxel in the treatment of any of these conditions.

Contraindications and Warnings

The current prescribing information for cabazitaxel (Jevtana, 2018) includes the following contraindications and black box warnings:

Contraindications:

Jevtana is contraindicated in individuals with:

Black Box Warnings:

Definitions

ECOG Performance Status: A scale used to determine the individual's level of functioning. This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale:

Metastatic: The spread of cancer from one part of the body to another. A metastatic tumor contains cells that are like those in the original (primary) tumor and have spread. 

References

Peer Reviewed Publications:

  1. Bahl A, Oudard S, Tombal B, et al.; TROPIC Investigators. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013; 24(9):2402-2408.
  2. Beer TM, Hotte SJ, Saad F, et al. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial. Lancet Oncol. 2017; 18(11):1532-1542.
  3. Bellmunt J, Kerst JM, Vazquez F, et al.; SOGUG and DUOS. 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; 28(7):1517-1522.
  4. de Bono JS, Oudard S, Ozguroglu M, et al.; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010; 376(9747):1147-1154.
  5. Eisenberger M, Hardy-Bessard AC, Kim CS, et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m(2)) and the currently approved dose (25 mg/m(2)) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol. 2017; 35(28):3198-3206.
  6. 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; 10(8):1221-1228.
  7. Ghoochani A, Hatipoglu Majernik G, et al. Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis. Oncotarget. 2016; 7(21):38306-38318.
  8. Girard E, Ditzler S, Lee D, et al. Efficacy of cabazitaxel in mouse models of pediatric brain tumors. Neuro Oncol. 2015; 17(1):107-115.
  9. Joshi A, Patil V, Noronha V, et al. Results of a phase II randomized controlled clinical trial comparing efficacy of cabazitaxel versus docetaxel as second line or above therapy in recurrent head and neck cancer. Oral Oncol. 2017; 75:54-60.
  10. Kang YK, Ryoo BY, Yoon S, et al. A phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA). Cancer Chemother Pharmacol. 2015; 75(2):309-318.
  11. Kummel 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; 84:1-8.
  12. Oudard S. TROPIC: phase III trial of cabazitaxel for the treatment of metastatic castration-resistant prostate cancer. Future Oncol. 2011; 7(4):497-506.
  13. Oudard S, Fizazi K, Sengelov L, et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial-FIRSTANA. J Clin Oncol. 2017; 35(28):3189-3197.
  14. Rixe O, Puzanov I, LoRusso PM, et al. Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies. Anticancer Drugs. 2015; 26(7):785-792.
  15. Villanueva C, Awada A, Campone M, et al. A multicentre dose-escalating study of cabazitaxel (XRP6258) in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment: a phase I/II study. Eur J Cancer. 2011; 47(7):1037-1045.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Urological Association (AUA). Castration-Resistant Prostate Cancer. Amended 2018. Available at: https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-(2013-amended-2018). Accessed on September 24, 2018.
  2. Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2014; 32(30):3436-3448.
  3. Cabazitaxel. In: DrugPoints® System (electronic version). Truven Health Analytics. Greenwood Village, CO. Updated April 30, 2018. Available at: http://www.micromedexsolutions.com. Accessed on September 24, 2018.
  4. Cabazitaxel Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised February 27, 2018. Accessed on September 24, 2018.
  5. Jevtana® (cabazitaxel) [Product Information], Bridgewater, NJ. Sanofi-Aventis U.S. LLC. January 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201023s021lbl.pdf. Accessed on September 24, 2018.
  6. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on September 24, 2018.
  7. NCCN Clinical Practice Guidelines in Oncology®. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on September 24, 2018.
    • Prostate Cancer (V.4.2018). Revised August 5, 2018.
Websites for Additional Information
  1. American Cancer Society. Key statistics for prostate cancer. Revised January 4, 2018. Available at: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed on September 24, 2018.
  2. National Cancer Institute. Prostate cancer treatment (PDQ®) – patient version. Last updated April 30, 2018. Available at: https://www.cancer.gov/types/prostate/patient/prostate-treatment-pdq#section/all. Accessed on September 24, 2018.
Index

Cabazitaxel
Jevtana

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed

11/08/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Reviewed

10/31/2018

Hematology/Oncology Subcommittee review. Updated Discussion/General Information, References, and Websites for Additional Information sections.

New

11/02/2017

MPTAC review. Initial document development.

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial document development. Moved content of DRUG.00102 Cabazitaxel (Jevtana®) to new clinical utilization management guideline document with the same title.