Medical Policy

 

Subject: Atezolizumab (Tecentriq®)
Document #: DRUG.00088 Publish Date:    08/29/2018
Status: Revised Last Review Date:    07/26/2018

Description/Scope

This document addresses the use of atezolizumab (Tecentriq) (Genentech, San Francisco, CA), an anti-programmed death ligand 1 (PD-L1) monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) for treatment of locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) under specific circumstances.

Note: Please see these documents for related topics:

Position Statement

Medically Necessary:

Urothelial Carcinoma

The use of atezolizumab is considered medically necessary for first-line treatment of locally advanced or metastatic urothelial carcinoma when the following criteria are met:

  1. Individual is ineligible for any platinum-containing chemotherapy; and
  2. For individuals who are not eligible for cisplatin-containing chemotherapy: tumor testing indicates that PD-L1 stained tumor-infiltrating immune cells cover expression greater than or equal to 5% of the tumor area, as determined by an FDA-approved test; and
  3. Individual has a current ECOG performance status of 0-2; and
  4. Individual has not received treatment with another PD-1 or PD-L1 agent (for example, nivolumab or pembrolizumab); and
  5. Individual is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

The use of atezolizumab is considered medically necessary for subsequent treatment of locally advanced or metastatic urothelial carcinoma when the following criteria are met:

  1. Disease has progressed during or following platinum-containing chemotherapy (for example, cisplatin); or
  2. Disease has progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and
  3. Individual has a current Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; and
  4. Individual has not received treatment with another PD-1 or PD-L1 agent (for example, nivolumab or pembrolizumab); and
  5. Individual is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Non-Small Cell Lung Cancer (NSCLC):

The use of atezolizumab is considered medically necessary for the first-line treatment of recurrent or metastatic nonsquamous NSCLC when the following criteria are met:

  1. When used in a combination regimen with carboplatin, paclitaxel, and bevacizumab; and
  2. When EGFR, ALK, ROS1, and BRAF are negative or unknown, and PD-L1 is less than 50% or unknown; and
  3. Individual has a current ECOG performance status of 0-1; and
  4. Individual is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

The use of atezolizumab is considered medically necessary for continuation maintenance therapy in combination with or without bevacizumab for recurrent or metastatic nonsquamous NSCLC when the following criteria are met:

  1. Individual achieved tumor response or stable disease following initial cytotoxic therapy (first-line atezolizumab/carboplatin;paclitaxel/bevacizumab regimen); and
  2. Individual has a current ECOG performance status of 0-2; and
  3. Individual is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

The use of atezolizumab is considered medically necessary for the subsequent treatment of metastatic NSCLC when the following criteria are met:

  1. Disease has progressed during or following platinum-containing chemotherapy (for example, cisplatin); and
  2. When anaplastic lymphoma kinase (ALK) or epidermal growth factor receptor (EGFR) genomic tumor aberrations are present, must have demonstrated disease progression on FDA-approved therapy; and
  3. Individual has a current ECOG performance status of 0-2; and
  4. Individual has not received treatment with another PD-1or PD-L1 agent (for example, nivolumab or pembrolizumab); and
  5. Individual is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Investigational and Not Medically Necessary:

The use of atezolizumab is considered investigational and not medically necessary when the above criteria are not met and for all other uses, including but not limited to:

Rationale

Urothelial Carcinoma

On May 18, 2016, the FDA approved atezolizumab for the treatment of individuals with locally advanced or metastatic urothelial cancer who had disease progression during or following platinum-containing chemotherapy or whose disease progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Subsequently, on April 17, 2017 the FDA approved atezolizumab for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. The indications were approved under an accelerated process based on tumor response rate and durability of response. The FDA stated that continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

In May 2018, the FDA issued a warning, based on data from the ongoing IMvigor130 trial (NCT02807636), that individuals “with PD-L1 low status had decreased survival” compared to individuals “who received cisplatin- or carboplatin-based chemotherapy” (FDA, 2018). As a result, the FDA amended the prescribing label to restrict first-line use to individuals who are not eligible for cisplatin-containing chemotherapy, whose tumors express PD-L1 as measured by PD-L1 stained tumor-infiltrating immune cells covering ≥ 5% of the tumor area, or are not eligible for any platinum-based chemotherapy regardless of tumor PD-L1 expression.

A phase I study (Powles, 2014) provided the initial evidence of the safety and efficacy of atezolizumab for the treatment of metastatic bladder cancer. Results of the phase I study were expanded into a multicenter, single-arm, phase II trial (NCT02108652) of individuals at least 18 years of age with inoperable locally advanced or metastatic urothelial carcinoma whose disease had progressed after previous platinum-based chemotherapy (Rosenberg, 2016). Key inclusion criteria were ECOG performance status of 0 or 1, measurable disease defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), adequate hematological and end-organ function, and no autoimmune disease, active infections, or corticosteroid use. Treatment consisted of intravenous atezolizumab (1200 mg every 3 weeks). The primary endpoint of the study was objective response rate based on both the independent review facility-assessed objective response rate and the investigator-assessed objective response rate. Between May 13, 2014 and Nov 19, 2014, 315 individuals from 70 major academic medical centers and community oncology practices in Europe and North America were enrolled into the study. Of the 315, a total of 310 received atezolizumab (5 enrollees later did not meet eligibility criteria and were not dosed with study drug). The primary analysis showed that, compared with a historical control overall response rate of 10%, treatment with atezolizumab resulted in a significantly improved RECIST v1.1 objective response rate for each prespecified immune cell group (IC2/3: 27% [95% confidence interval (CI), 19-37], p<0.0001; IC1/2/3: 18% [13-24], p=0.0004) and in all subjects (15% [11-20], p=0.0058). Of note, the objective response rate was 8% in subjects who were classified as “negative” for PD-L1 expression lower than historical control objective response rate. At longer follow-up of all 310 subjects, objective response rates were 26% (95% CI, 18-36) in the IC2/3 group, 18% (13-24) in the IC1/2/3 group, and 15% (11-19) overall in all 310 subjects. At a median follow-up of 11.7 months (95% CI, 11.4-12.2), ongoing responses were recorded in 38 (84%) of 45 subjects. The Cancer Genome Atlas (TCGA) subtypes and mutation load were found to be independently predictive for response to atezolizumab. Grade 3-4 treatment-related adverse events, of which fatigue was the most common (5 individuals [2%]), were low and occurred in 50 (16%) of 310 treated subjects. There were no cases of febrile neutropenia. A total of 15 (5%) of 310 treated subjects had grade 3-4 immune-mediated adverse events, with pneumonitis, increased aspartate aminotransferase, increased alanine aminotransferase, rash, and dyspnea being the most common. There were no treatment-related deaths during the study. The authors concluded that atezolizumab showed durable activity and good tolerability in this particular population.

A single-arm, multi-center phase II trial (Balar, 2017) studied the safety and efficacy of atezolizumab as first-line chemotherapy for cisplatin-ineligible, locally advanced or metastatic urothelial carcinoma. A total of 47 academic medical centers and community oncology practices in seven countries participated. Cohort 1 consisted of subjects without previous treatment for metastatic urothelial cancer. Eligibility criteria included: inoperable, locally advanced or metastatic urothelial cancer (renal pelvis, ureters, bladder or urethra), measurable disease per RECIST, a tumor sample available for PD-L1 testing, and an ECOG performance status of 2 or less. Cisplatin ineligibility was defined as having one or more of the following: glomerular filtration rate (GFR) more than 30 mL/min and less than 60 mL/min (Cockcroft-Gault formula), a hearing loss measured by audiometry of 25 dB at two contiguous frequencies, grade 2 or greater peripheral neuropathy (that is, sensory alteration or paresthesias including tingling), or an ECOG performance score of 2. Cohort II was described earlier by Rosenberg and colleagues (2016) and had enrolled subjects previously treated with platinum-based chemotherapy. A total of 123 subjects were enrolled between June 9, 2014 and March 30, 2015. Of those, 119 were treated with at least one dose of intravenous atezolizumab every 21 days until unacceptable toxicity or investigator-assessed radiographic progression. At 17.2 months median follow-up, the objective response rate was 23% (95% CI, 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival (PFS) was 2.7 months (2.1 to 4.2). Median overall survival (OS) was 15.9 months (10.4 to not estimable). Tumor mutation load was associated with response. A total of 114 (96%) of subjects had an adverse event and 79 (66%) had a treatment-related event. Treatment-related adverse events that occurred in at least 10% of subjects were fatigue, diarrhea and pruritus. One treatment-related death due to sepsis was reported. Adverse events leading to discontinuation of treatment occurred in 9 subjects and immune-mediated events occurred in 14 (12%) subjects. The authors concluded “overall, atezolizumab showed promising response durability and survival, coupled with a low incidence of clinically relevant toxicities despite numerous comorbidities in this population.”

Powles and colleagues (2018) conducted IMvigor211, an industry-supported, multicenter, phase III, open-label randomized controlled trial to compare atezolizumab to chemotherapy by PD-L1 expression for individuals with platinum-treated metastatic urothelial carcinoma. Between January 13, 2015 and February 15, 2016, researchers randomized 931 subjects to receive atezolizumab (n=467) or chemotherapy (n=464). Subjects were from 217 academic medical centers in mostly Europe, North America, and the Asia-Pacific region. Eligibility criteria included age 18 years or older, measurable metastatic urothelial carcinoma at baseline as defined by RECIST, ECOG performance status of 0 or 1, evaluable sample for PD-L1 testing (regardless of PD-1 status), no more than two previous lines of therapy, progression during or following one or more platinum-containing regimens (or neoadjuvant or adjuvant therapy with progression within 12 months), and a predominance of transitional histology. Exclusion criteria included previous autoimmune disease, previous therapies targeting CD137, CTLA4, or PD-L1-PD-1, symptomatic brain metastasis, and inadequate renal or liver function. Every 3 weeks (until unacceptable toxicity, RECIST progression, or withdrawn consent), subjects received either atezolizumab 1200 mg or physician-selected chemotherapy that was selected before randomization and was not previously given to the subject (vinflunine, paclitaxel, or docetaxel). The researchers stratified randomization by PD-L1 expression (expression on < 1% [IC0] or 1% to < 5% [IC1] of tumour-infiltrating immune cells vs ≥ 5% of tumour-infiltrating immune cells [IC2/3]), chemotherapy type, liver metastases, and additional prognostic factors. Subjects and investigators were masked to PD-L1 expression status but were aware of group allocation. The primary endpoint was OS, defined as the time from randomization to death, in a hierarchy of prespecified populations (IC2/3, IC1/2/3, intention-to-treat). The median OS in individuals with IC2/3 PD-L1 expression levels (n=234) was 11.1 months for the atezolizumab group and 10.6 months for the chemotherapy group (p=0.41). In addition, the objective response rate (ORR) was not significant between the two groups (23% versus 22%). However, the atezolizumab group had less grade 3 or 4 adverse events (20% versus 43%) and had a longer duration of response (15.9 months versus 8.3 months). The researchers found that the “primary endpoint of overall survival improvement with atezolizumab was not met in patients with metastatic urothelial carcinoma with at least 5% PD-L1 expression on tumour-infiltrating immune cells, precluding additional formal statistical analysis.” The IMvigor211 study is ongoing but no longer recruiting (NCT02302807).

The National Comprehensive Cancer Network (NCCN) Bladder Cancer Guidelines (V5.2018) and 2018 NCCN Drug Compendium currently indicate that atezolizumab may be used for first-line systemic therapy (cisplatin-ineligible individuals who have tumors expressing PD-L1 [PD-L1 stained tumor-infiltrating immune cells covering ≥ 5% of the tumor area] or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression) (2A recommendation) or second-line for locally advanced or metastatic disease (2A recommendation) under specific conditions.

Non-Small Cell Lung Cancer (NSCLC)

On October 18, 2016 the FDA approved atezolizumab for treatment of metastatic NSCLC with disease progression during or following platinum-containing chemotherapy. The current 2018 prescribing information indicates that “patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Tecentriq.” Similar drugs for this indication are Opdivo and Keytruda. The FDA’s approval was based on positive results of the randomized phase III OAK (NCT02008227) and phase II POPLAR (NCT01903993) studies. The OAK trial (Rittmeyer, 2017) investigated the safety and effectiveness of atezolizumab as compared to docetaxel in 1225 individuals. The primary analysis population consisted of the first 850 randomized subjects. Median overall survival for the atezolizumab group (n=425) was 13.8 months compared to 9.6 months for those treated with docetaxel (n=425).

The POPLAR trial (open-label, multicenter, randomized study to investigate the efficacy and safety of atezolizumab compared with docetaxel in patients with non-small cell lung cancer after platinum failure) (NCT01903993) by Fehrenbacher and colleagues (2016) studied the safety and efficacy of atezolizumab versus docetaxel. This phase II trial consisted of individuals with NSCLC who progressed on post-platinum chemotherapy that were recruited from 61 academic medical centers and community oncology practices in 13 countries in Europe and North America. Key inclusion criteria were ECOG performance status 0 or 1, measurable disease by RECIST v1.1, and adequate hematological and end-organ function. Key exclusion criteria were autoimmune or chronic viral diseases, active or untreated CNS metastases, history of pneumonitis, or previous treatment with docetaxel, CD137 agonists, anti-CTLA4, anti-PD-L1, or anti-PD-L1 therapeutic antibodies, or PD-L1-PD1 pathway-targeting agents. Individuals were stratified by PD-L1 tumor-infiltrating immune cell status, histology, and previous lines of therapy, and randomly assigned (1:1) to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m2 once every 3 weeks. The primary endpoint was OS in the intention-to-treat population and PD-L1 subgroups at 173 deaths. Between Aug 5, 2013 and March 31, 2014, a total of 144 subjects were randomized to the atezolizumab group, and 143 to the docetaxel group. Of these, 142 individuals received at least one dose of atezolizumab and 135 received docetaxel. OS in the intention-to-treat population was 12.6 months (95% CI, 9.7-16.4) for atezolizumab versus 9.7 months (8.6-12.0) for docetaxel (hazard ratio [HR] 0.73 [95% CI, 0.53-0.99]; p=0.04). OS in individuals without PD-L1 expression in either tumor cells or tumor-infiltrating immune cells in the atezolizumab group was similar to that in the docetaxel group. An increase in OS was associated with increasing PD-L1 expression. In the exploratory analysis, individuals with pre-existing immunity had improved OS with atezolizumab. A total of 11 (8%) subjects in the atezolizumab group discontinued because of adverse events versus 30 (22%) subjects in the docetaxel group. Additionally, 16 (11%) subjects in the atezolizumab group versus 52 (39%) subjects in the docetaxel group had treatment-related grade 3-4 adverse events, and 1 (< 1%) subject in the atezolizumab group versus 3 (2%) subjects in the docetaxel group died from a treatment-related adverse event. The authors concluded that atezolizumab significantly improved survival compared with docetaxel in individuals with previously treated NSCLC. Improvement correlated with PD-L1 immunohistochemistry expression on tumor cells and tumor-infiltrating immune cells, suggesting that PD-L1 expression is predictive for atezolizumab benefit.

In the phase II, multicenter, open-label, single-arm BIRCH trial, Peters and colleagues (2017) examined the efficacy and safety of atezolizumab as a first-line or subsequent therapy for individuals with advanced (PD-L-selected stage IIIB/IV) NSCLC. A total of 659 subjects were categorized into 3 cohorts: no prior chemotherapy for advanced NSCLC (cohort 1; first-line), progression during or following no more than one prior platinum-based regimen for advanced NSCLC (cohort 2; second-line), or progression during or following at least two prior chemotherapy regimens for advanced NSCLC (cohort 3; third line or above). Inclusion criteria included confirmed stage IIIB/IV or recurrent NSCLC, age ≥ 18 years, tumor PD-L1 expression, ECOG performance status 0 or 1, measurable disease per RECIST version 1.1, and adequate hematologic and end-organ function. The primary endpoint was independent review facility (IRF)-assessed objective response rate, and the secondary endpoints were duration of response and progression-free survival. The median duration of treatment was 4.2 months, and the drug was discontinued in 520 subjects: progressive disease (65%), adverse events (7%), subject’s decision (3%), protocol deviation (2%), or physician decision (1%). Subjects were followed for a minimum of 12 months. For cohorts 1, 2, and 3, the objective response rate was 22%, 19%, and 18%, respectively. The objective response rate was higher in smokers and those with nonsquamous NSCLC. For cohorts 1, 2, and 3, the duration of response was 9.8 months, not estimable, and 11.8 months, respectively. The progression-free survival was higher for cohort 1 (5.4 months; 95% CI, 3.0 to 6.9) than cohort 2 (2.8 months; 95% CI, 1.5 to 3.9) or cohort 3 (2.8 months; 95% CI, 2.7 to 3.0). The median survival for all treated subjects was 14.6 months. At least 1 adverse event was experienced in 94% of subjects, and serious adverse events included pneumonia (4%), dyspnea (3%), pyrexia (3%), and pneumonitis (2%). Death occurred in 305 (46%) subjects, mostly due to disease progression. The researchers concluded that atezolizumab was beneficial for advanced NSCLC, but large, randomized trials are needed.

Socinski and colleagues (2018) conducted IMpower150, an industry-sponsored, multicenter, international, open-label, phase 3, randomized study to evaluate the combination of atezolizumab and bevacizumab, along with chemotherapy, for first-line treatment in individuals with NSCLC. Inclusion criteria included stage IV or recurrent metastatic non-squamous NSCLC (classified according to RECIST and not previously treated with chemotherapy), ECOG performance status of 0-1, tissue biomarker testing for bevacizumab eligibility, any PD-L1 immunohistochemistry status, and the presence of EGFR or ALK alterations when tyrosine kinase inhibitor therapy did not stop disease progression or caused unacceptable side effects. Exclusion criteria included a history of untreated metastases of the central nervous system, a history of autoimmune disease, previous immunotherapy or anti-CTLa-4 therapy within 6 weeks before randomization, or systemic immunosuppressive medications within 2 weeks before randomization. A total of 1202 subjects (240 sites, 26 countries) were randomized into 3 regimen groups: 1) atezolizumab, carboplatin, and paclitaxel (ACP group; n=402); 2) atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP group; n=400); and 3) bevacizumab, carboplatin, and paclitaxel (BCP group; n=400). Subjects were given 4 or 6 cycles (21 days each cycle) with the following dosages: atezolizumab 1200 mg, bevacizumab 15 mg per kg/body weight, paclitaxel 200 mg per square meter of body-surface area (175 mg per square meter for Asian subjects), and carboplatin 6 mg per ml per minute area under the concentration-time curve. The primary endpoint included investigator-assessed progression-free survival in both the wild-type (WT) genotype population (subjects with EGFR or ALK alterations excluded) and the Teff-high WT population (subjects with a high expression of an effector T-cell (Teff) gene signature in the tumor). In addition, a primary endpoint was the overall survival in the WT population (n=1040). Subjects were assessed at screening, every 6 weeks for 48 weeks, and every 9 weeks until disease progression or until benefit was lost. The minimum duration of follow-up was 9.5 months. For the WT population, the median progression-free survival was longer for the ABCP group than the BCP group (8.3 months versus 6.8 months; HR for disease progression of death, 0.62; 95% CI, 0.52 to 0.74; p<0.001). Likewise, the progression-free survival was longer for the ABCP group than the BCP group in the Teff-high WT population (11.3 months versus 6.8 months; HR, 0.51; 95% CI, 0.38 to 0.68; p<0.001). The median overall survival for the WT ABCP group was longer than the BCP group (19.2 months versus 14.7 months; HR, 0.78; 95% CI, 0.64 to 0.96; p=0.02). Adverse events occurred in 94.4% of the ABCP group and 95.4% of the BCP group, and deaths related to treatment occurred in 11 ABCP subjects (2.8%) and 9 BCP subjects (2.3%). Immune-related adverse events occurred in 77.4% of the ABCP group, the most common being rash, hepatitis, hypothyroidism, hyperthyroidism, pneumonitis, and colitis. The researchers concluded that the study “showed that the addition of atezolizumab to bevacizumab plus chemotherapy as first-line treatment for nonsquamous metastatic NSCLC resulted in a significant improvement in progression-free survival and overall survival, regardless of PD-L1 expression and EGFR or ALK genetic alteration status.”

The NCCN NSCLC guidelines (V5.2018) and the 2018 NCCN Drug Compendium indicate that atezolizumab may be used for the treatment of NSCLC following progression of metastatic disease (category 1 recommendation), for first-line treatment when given with a regimen of carboplatin, paclitaxel, and bevacizumab (category 1 recommendation), and for continuation maintenance (category 1 recommendation) under specific conditions.

Other Potential Uses

Other indications under investigation include breast cancer (García-Teijido, 2016); gastric cancer (Alsina, 2016); renal cancer (McDermott, 2016); colorectal cancer; soft tissue sarcoma, diffuse large B cell lymphoma, follicular lymphoma, hematological malignancies, malignant melanoma (Mahoney, 2015), multiple myeloma and myelodysplastic syndromes. The largest published study from this group is a phase 1 clinical trial by McDermott and colleagues (2016) of 63 individuals with renal cancer treated with atezolizumab. Although initial study results show potential promise, large randomized clinical trials are needed for further evaluation. At this time the published evidence supporting the use of atezolizumab is insufficient to demonstrate safety and efficacy for all uses other than for urothelial and NSCLC under specific circumstances.

Background/Overview

 

Urothelial carcinoma is the most common type of bladder cancer and occurs in the urinary tract system, involving the bladder and related organs. The American Cancer Society estimates that in 2018 there will be approximately 81,190 new cases of bladder cancer (about 62,380 in men and 18,810 in women) and 17,240 deaths from bladder cancer (about 12,520 in men and 4720 in women) in the United States.

Non-small cell lung cancer is the most common type of lung cancer. Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women (not counting skin cancer). In men, prostate cancer is more common, while in women breast cancer is more common. About 14% of all new cancers are lung cancers. The American Cancer Society estimates that in 2018 there will be about 234,030 new cases of lung cancer (121,680 in men and 112,350 in women) and 154,050 deaths from lung cancer (83,550 in men and 70,500 in women) in the United States. Lung cancer is by far the leading cause of cancer death among both men and women; about 1 out of 4 cancer deaths are from lung cancer. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined.

Tecentriq (atezolizumab) 2018 FDA Product Information label includes the following warnings and precautions:

Most common adverse reactions (≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma were fatigue, decreased appetite, nausea, constipation, urinary tract infection, diarrhea, and pyrexia.

Most common adverse reactions (≥ 20%) in patients with metastatic non-small cell lung cancer were fatigue, decreased appetite, dyspnea, and cough.

Use in specific populations: Lactation: Advise women not to breastfeed during treatment and for at least 5 months after the last dose.

Along with Tecentriq, the FDA simultaneously issued a premarket approval (PMA) for the Ventana PD-L1 (SP142) Assay (Ventana Medical Systems, Tucson, Arizona) as a complementary diagnostic test. The FDA noted that the immunohistochemistry test "may help identify patients who are more likely to respond to treatment.” Unlike companion diagnostics, which may be necessary for the effective and safe use of a drug, complementary diagnostics are intended to aid but are not required to guide treatment strategies.

Definitions

Adjuvant treatment: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

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:

Line of therapy:

Locally advanced cancer: Cancer that has spread from where it started to nearby tissue or lymph nodes.

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.

Neoadjuvant treatment: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy.

Coding

The following codes for treatments and procedures applicable to this document 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.

When services may be Medically Necessary when criteria are met:

HCPCS

 

J9022

Injection, atezolizumab, 10 mg [Tecentriq]

 

 

ICD-10 Diagnosis

 

 

C34.00-C34.92

Malignant neoplasm of bronchus and lung

 

C61

Malignant neoplasm of prostate

 

C65.1-C65.9

Malignant neoplasm of renal pelvis

 

C66.1-C66.9

Malignant neoplasm of ureter

 

C67.0-C67.9

Malignant neoplasm of bladder

 

C68.0

Malignant neoplasm of urethra

 

Z85.118

Personal history of other malignant neoplasm of bronchus and lung

 

Z85.51

Personal history of malignant neoplasm of bladder

 

Z85.53-Z85.54

Personal history of malignant neoplasm of renal pelvis, ureter

 

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Alsina M, Moehler M, Hierro C, et al. Immunotherapy for gastric cancer: a focus on immune checkpoints. Target Oncol. 2016; 11(4):469-477.
  2. Balar AV, Galsky MD, Rosenberg JE, et al; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017; 389(10064):67-76.
  3. Fehrenbacher L, Spira A, Ballinger M, et al.; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016; 387(10030):1837-1846.
  4. García-Teijido P, Cabal ML, Fernández IP, Pérez YF. Tumor-infiltrating lymphocytes in triple negative breast cancer: the future of immune targeting. Clin Med Insights Oncol. 2016; 10(Suppl 1):31-39.
  5. Mahoney KM, Freeman GJ, McDermott DF. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther. 2015; 37(4):764-782.
  6. McDermott DF, Sosman JA, Sznol M, et al. Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol. 2016; 34(8):833-842.
  7. Peters S, Gettinger S, Johnson ML, et al. Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed death-ligand 1-selected advanced non-small-cell lung cancer (BIRCH). J Clin Oncol. 2017; 35(24):2781-2789.
  8. Powles T, Durán I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018; 391(10122):748-757.
  9. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014; 515(7528):558-562.
  10. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017; 389(10066):255-265.
  11. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387(10031):1909-1920.
  12. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018; 378(24):2288-2301.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Atezolizumab. In: DrugPoints System [Electronic Version]. Truven Health Analytics. Greenwood Village, Colo. Last updated June 20, 2018. Available at: http://www.micromedexsolutions.com. Accessed on July 3, 2018.
  2. Atezolizumab Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised June 20, 2018. Accessed on July 3, 2018.
  3. Hoffmann-La Roche. Study of atezolizumab as monotherapy and in combination with platinum-based chemotherapy in participants with untreated locally advanced or metastatic urothelial carcinoma (IMvigor130). NLM Identifier: NCT02807636. Last updated on June 25, 2018. Available at: https://www.clinicaltrials.gov/‌ct2/show/‌NCT02807636?cond=NCT02807636&rank=1. Accessed on July 3, 2018.
  4. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on June 29, 2018.
  5. NCCN Clinical Practice Guidelines in Oncology™. © 2016 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on July 3, 2018.
    • Bladder Cancer. V5.2018. Revised July 3, 2018.
    • Non-Small Cell Lung Cancer. V5.2018. Revised June 27, 2018.
  6. Tecentriq™ [Product Information]. South San Francisco, CA. Genentech, Inc. July 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761034s012lbl.pdf. Accessed on July 3, 2018.
  7. U.S. Food and Drug Administration Premarket Approval (PMA) Database. Ventana PD-L1(SP142) CDX Assay. Rockville, MD: FDA. May 18, 2016. Available at: http://www.accessdata.fda.gov/scripts/cdrh/‌cfdocs/cfpma/pma.cfm?id=P160002. Accessed on July 3, 2018.
  8. U.S. Food and Drug Administration. Keytruda (pembrolizumab) or Tecentriq (atezolizumab): FDA alerts health care professionals and investigators: FDA statement - decreased survival in some patients in clinical trials associated with monotherapy. May 18, 2018. Available at: https://www.fda.gov/Safety/MedWatch/‌SafetyInformation/‌SafetyAlertsforHumanMedicalProducts/ucm608253.htm. Accessed on July 3, 2018.
Websites for Additional Information
  1. American Cancer Society. Bladder Cancer. Available at: http://www.cancer.org/cancer/‌bladdercancer/‌detailedguide/‌index. Accessed on July 3, 2018.
  2. American Cancer Society. Lung Cancer - Non-Small Cell. Available at: http://www.cancer.org/‌Cancer/LungCancer-Non-SmallCell/‌DetailedGuide/index. Accessed on July 3, 2018.
Index

Anti-PD-L1 Monoclonal Antibody
Atezolizumab
MPDL3280A
MPDL 3280A
Tecentriq

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.

Document History

Status

Date

Action

Revised

07/26/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Revised

07/18/2018

Hematology/Oncology Subcommittee review. Medically Necessary statement expanded for first-line urothelial carcinoma. Medically Necessary statements added for first-line and continuation maintenance therapy for nonsquamous NSCLC. Rationale, References, and Websites sections updated.

Reviewed

05/03/2018

MPTAC review.

Reviewed

05/02/2018

Hematology/Oncology Subcommittee review. Rationale, References, and Websites sections updated.

 

12/27/2017

The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 HCPCS changes;  added J9022, removed C9483 deleted 12/31/2017 and NOC codes.

Revised

05/04/2017

MPTAC review.

Revised

05/03/2017

Hematology/Oncology Subcommittee review. Trademark symbol in title of document replaced with the registered symbol. Medically necessary statements reformatted. Added a medically necessary statement for first-line treatment of locally advanced or metastatic urothelial carcinoma. Added PD-L1 to existing criteria as an agent that the individual has not received treatment with. Rationale, Background and References sections updated.

Revised

11/03/2016

MPTAC review.

Revised

11/02/2016

Hematology/Oncology Subcommittee review. Medically Necessary statement added for metastatic NSCLC. Removed “solid tumors” from the Investigational and Not Medically Necessary list. Description, Rationale, Background, Coding and Reference sections updated.

 

10/01/2016

Updated Coding section with 10/01/2016 HCPCS changes.

New

07/27/2016

MPTAC review.

New

07/12/2016

Hematology/Oncology Subcommittee review. Initial document development.