The main purpose of the study is to learn how the lung cancer medicines work. The study also looks into treatment sequence of these medicines. This study is performed outside of clinical studies in a database in the United States in patients with metastatic or advanced non-small cell lung cancer. Non-small cell lung cancer is a group of lung cancers named for the kinds of cells found in the cancer and how the cells look under a microscope. Metastasis is when the cancer cells spread to other parts of the body. Advanced cancer is when the patient is diagnosed with stage III or stage IV cancer.

This study includes patient's information from the database who:

• Are aged 18 years or older.
• Are confirmed to have metastatic non-small cell lung cancer on or after 1 January 2021.
• Have a positive Anaplastic Lymphoma Kinase (ALK) gene mutation or rearrangement. A gene is a part of your DNA that has instructions for making things your body needs to work and a mutation or rearrangement can cause the gene not to work properly. ALK is a protein that helps control cell growth.
• Received lorlatinib as their first treatment.

All participants in this study had received the study medicine lorlatinib. It is a tablet that is taken by mouth at home. They continued to take the study medicine until their cancer was no longer responding. The study will look at the experiences of people receiving the study medicine.

The study is based on information collected from Flatiron Health's Advanced NSCLC Panoramic dataset which includes:

- Diagnosis, cancer stage at diagnosis, date of diagnosis, birth year, type of medicinal treatment, date of treatment start and end, age, gender, etc.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer diagnoses worldwide, most often diagnosed in advanced stages. Targeted drugs are currently the most often used therapies for advanced NSCLC patients that harbor rearrangements in the anaplastic lymphoma kinase (ALK) gene, defining a distinct molecular subtype with unique therapeutic considerations. The development of ALK targeted tyrosine kinase inhibitors (TKIs) has substantially improved outcomes for patients with advanced or metastatic NSCLC with these genetic variants. Lorlatinib, a third-generation inhibitor, is a potent TKI that is effective resistance to first- and second-generation ALK-TKIs. Based on the results of the pivotal phase III clinical trial, lorlatinib received regulatory approval for first line treatment of ALK positive metastatic NSCLC on 3 March 2021, establishing it as an important treatment option in routine clinical practice.

While randomized clinical trials provide critical evidence of efficacy and safety under controlled conditions, patients treated in real world settings may differ from trial populations with respect to baseline characteristics, comorbidities, treatment sequencing, and clinical management. Data describing duration of therapy and frequency of dose modifications as well as other clinical characteristics such as Eastern Cooperative Oncology Group (ECOG) performance status over time would help to elucidate the patient experience in the real-world as a first step while longer durations of follow-up time continue to accumulate.

The objective of this non-interventional study is to generate real-world evidence (RWE) characterizing 1L lorlatinib use among adults in the United States (US) using routinely collected electronic health record (EHR) data. This is a retrospective longitudinal cohort study of patients diagnosed with advanced/metastatic NSCLC with an ALK rearrangement treated with 1L lorlatinib after its approval on 3 March 2021 in the United States.

Inclusion Criteria:

• Positive for ALK rearrangement
• 18 years or older at advanced/metastatic NSCLC diagnosis date
• Initiated 1L lorlatinib in the metastatic/advanced setting between 3 March 2021 and latest data cutoff available

Exclusion Criteria:

• Missing ALK rearrangement status
• Use of alectinib in the adjuvant setting
• Use of lorlatinib in a clinical trial setting

The study population are patients with advanced/metastatic non-small cell lung cancer in Flatiron Health's Advanced NSCLC Panoramic dataset.

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.