Study on impact of scanning intervals of follow up tumor assessments on Progression Free Survival (PFS) and median PFS for Non-Small Cell Lung Cancer (NSCLC) patients treated with Atezolizumab and Docetaxel

Lead Investigator: Lena Friberg, Uppsala University
Title of Proposal Research: Study on impact of scanning intervals of follow up tumor assessments on Progression Free Survival (PFS) and median PFS for Non-Small Cell Lung Cancer (NSCLC) patients treated with Atezolizumab and Docetaxel
Vivli Data Request: 9478
Funding Source: Swedish Cancer Soceity
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Globally, lung cancer is a leading cause of cancer malignancy-related deaths. Approximately 80-85% of all lung cancer cases are a type of cancer known as non-small cell lung Cancer (NSCLC). Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It’s a condition where abnormal cells grow uncontrollably in the lungs. It usually grows and spreads more slowly than small-cell lung cancer. The three main types of non-small cell lung cancer are adenocarcinoma (most common), squamous cell carcinoma, and large cell carcinoma.
According to Cancer Net, in 2020, an estimated 2.3 million adults worldwide were diagnosed with lung Cancer, 80% of which was NSCLC. The five-year survival rates from standard treatments vary from 5%-55%, depending on the stage of the disease. However, with the intervention of immunotherapies, an increase of over 15% in long term survival has been observed.
Atezolizumab is a type of immunotherapy drug designed to target tumors with a protein marker known as Programmed death-ligand 1 (PDL1). These therapies work by restoring the immune cells, which then effectively eliminate tumor cells. Atezolizumab is approved as follow up therapy for NSCLC adult patients after surgery and chemotherapy. Additionally, it has received approval as a primary therapy for NSCLC patients whose tumors exhibit more than 50% of the PDL1 marker.
Docetaxel is a type of chemotherapy that stops tumor cells from growing. It’s often the choice of treatment when advanced lung cancer patients stop responding to other treatments. This drug is used as a second or third treatment option for lung cancer that has spread to other organs in the body. Docetaxel is also given to platinum-based chemotherapy failed lung cancer patients. Platinum-based chemotherapy is a treatment for lung cancer that utilizes drugs containing platinum to target and damage cancer cells’ DNA, hindering their ability to grow and spread. Though effective, it often comes with side effects like nausea, hair loss, and fatigue, affecting both cancerous and healthy cells.
Docetaxel can be used in combination with another chemotherapy drug named cisplatin for patients who have no prior anti-cancer treatments.

Compared to chemotherapies, immunotherapies like atezolizumab have shown to cause notable improvements in good response, survival rates and the overall quality of life. In cancer investigational treatments, doctors consider Overall Survival (OS) as the main measure to understand whether a treatment is working or not. OS is the golden standard as far as clinical outcomes are concerned. However, the U.S. food and drug administration (FDA) accepts progression free survival (PFS) as a valid measure for faster approvals in case of advanced cancers .

Progression-free Survival (PFS) is the duration of the time from when a patient starts a new treatment to when their disease starts getting worse or they succumb to death. Median PFS is an important measure that reports the time at which half of the people in the study had their disease get worse or died.

PFS is being preferred over OS as an outcome of interest because PFS helps to understand the effectiveness of a treatment faster and it’s not marred by other treatments which patients seek later. Moreover, the recent anti-cancer treatments are more about reducing the growth rate of the tumor or stopping its growth rather than completely curing the cancer. Thus, it makes sense to consider PFS as the outcome of choice.

In a clinical trial, regular checkups are done during and after the treatment cycles to understand how well the treatment is working. During these scheduled visits, the response of the tumors is assessed by taking images using imaging techniques such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) scans. CT scans use X-rays to create detailed images inside the body, while MRI scans use magnets and radio waves for similar purposes. PET scans involve a small amount of radioactive material to show how organs and tissues are functioning, particularly in detecting and monitoring cancer.

These scans help researchers to analyze if the tumors are responding to the therapy and helps calculate the PFS as well. These decisions are based on a set of guidelines called Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). According to RECIST, the disease is considered to be getting worse if the size of the tumors increases by at least 20%, along with appearance of new tumors, or increase in the size of unmeasurable baseline tumors.

In clinical trials and clinical practice settings, it is not possible to detect when the actual change in the size of the tumor occurred. The increase or decrease in the tumor size is generally reported during a scheduled trial appointment or a routine clinical checkup. So, the date when the change is observed in the scans is reported as a substitute for the actual time when the progression happened. There are however limited rules on how often these scans should be scheduled for advanced cancers. Doctors usually decide based on their judgment, with some general guidance from organizations like the US National Comprehensive Cancer Network .

In this research project, we will therefore look into how the scanning interval affects the clinical outcomes of interest namely PFS curves and median PFS. We will study platinum chemotherapy failed NSCLC patients who have received treatments namely, atezolizumab or docetaxel.

We will analyze in detail the data on how tumor size changes in patients and how the scanning interval helps in tracking the change. This includes analyzing tumor measurements and the overall response category. We want to study in detail how the timing of these scans and tumor assessments affects the results mentioned above (median PFS). Eventually, we hope to be able to recommend an appropriate tumor assessment frequency which works best for lung cancer patients both in clinical trials and practice.

Requested Studies:

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02008227
Sponsor ID: GO28915

A Phase II, Open-label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of MPDL3280A (Anti−PD-L1 Antibody) Compared With Docetaxel in Patients With Non−Small Cell Lung Cancer After Platinum Failure
Data Contributor: Roche
Study ID: NCT01903993
Sponsor ID: GO28753