Brazilian Lung Immunotherapy Study

Study Overview
=================
Brief Summary
-----------------
Immunotherapy with anti-PD-1/PD-L1 agents either as single agents or combined with chemotherapy is now considered the standard of care for patients with non-small-cell lung cancer. However, it has not been incorporated in the Brazilian Public Health System because of concerns about patient eligibility, safety and costs. It is known that simple biomarkers can be used to select patients for immunotherapy, such as EGRF, ALK and PD-L1 status in the tumors. We created a treatment protocol based on these 3 markers and treated 154 patients with non-small-cell-lung cancer in a Public Hospital in Brazil. The goal of this project is to identify the prevalence of these markers in the Brazilian population (to estimate patient eligibility), outcomes and costs of therapy.

Detailed Description
-----------------
Patients with metastatic non-small-cell lung cancer will undergo tumor testing for EGFR (by PCR), ALK and PD-L1 (by immunohistochemistry) and receive therapy based on these results. Patients with ALK-translocated tumors will receive first-line therapy with Alectinib, second-line therapy with carboplatin and pemetrexed and third-line therapy with docetaxel Patients with EGFR-mutated tumors will receive first-line therapy with Erlotinib, second-line therapy with carboplatin and pemetrexed and third-line therapy with docetaxel Patients with ALK/EGFRwt tumors and PD-L1>=50% will receive first-line pembrolizumab, second-line carboplatin-pemetrexed and third line docetaxel Patients with ALK/EGFRwt tumors and PD-L1<50% will receive first-line carboplatin-pemetrexed, second-line nivolumab and third line docetaxel. Therapy costs will be estimated, including hospital admissions and reported for each treatment arm.

Official Title
-----------------
Evaluation of Costs and Outcomes of the Implementation of Treatment Protocol Based on Rational Utilization of Anti-PD1 Agents in Patients With Non-small-cell Lung Cancer in the Brazilian Public Health System

Conditions
-----------------
Lung Neoplasm

Intervention / Treatment
-----------------
* Drug: Alectinib
* Drug: Pembrolizumab
* Drug: Nivolumab
* Drug: Erlotinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Stage IIIc or IV Non-small cell lung cancer Good performance status (ECOG 0-2) Available tissue for tumor markers Plan to undergo systemic therapy Exclusion Criteria: Inadequate cardiac, renal, liver of bone-marrow function Plan to undergo definitive radiation or curative surgery Consent withdraw

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients are treated in one of 4 different arms based on biomarker testing. There is no randomization or cross-over
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALK-translocated<br>st line Alectinib nd line Carboplatin pemetrexed rd line Docetaxel | Drug: Alectinib<br>* 600mg 1OD<br>* Other names: Alecensa;|
| Active Comparator: EGFR-mutant<br>st line Erlotinib nd line Carboplatin pemetrexed rd line Docetaxel | Drug: Erlotinib<br>* 150mg<br>* Other names: Tarceva;|
| Active Comparator: PD-L1 >= 50%<br>st line Pembrolizumab nd line Carboplatin pemetrexed rd line Docetaxel | Drug: Pembrolizumab<br>* 200mg every 21 days<br>* Other names: Keytruda;|
| Active Comparator: PD-L1< 50%<br>st line Carboplatin pemetrexed nd line nivolumab rd line Docetaxel | Drug: Nivolumab<br>* 6mg/kg every 4 weeks<br>* Other names: Opdivo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total cost of therapy | Sum of all direct costs involved in patient care, including admissions | Up to 3 years after starting systemic therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival | Median survival from first systemic therapy | Up to 3 years after starting systemic therapy | 
| Prevalence of ALK, EGFR, PD-L1>=50% | Prevalence of the 3 biomarkers in an unselected NSCLC population in Brazil | Up to 3 years after starting systemic therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-small cell lung cancer, NSCLC, Lung adenocarcinoma, Squamous cell carcinoma of the lung, Immunotherapy, PD-1, Nivolumab, Pembrolizumab