This study will collect data on Canadian cancer patients that have uncommon/rare changes in their tumours, such as alterations/rearrangements in the genetic material inside cells - known as deoxyribonucleic acid, or DNA, which acts as a map and gives directions to the cells on how to make other substances the body needs - because some of these changes have been found to respond to different drugs that help to stop the cancer. These rare changes occur in genes such as but not limited to ALK, EGFR, ROS1, BRAF, and NTRK which have targeted drugs in a family known as tyrosine kinase inhibitors (TKIs), and KRAS G12C mutation, which now has a targeted inhibitor drug therapy for patients with non small cell lung cancer (NSCLC). The goals for the study are to compare the natural history of such cancers and the treatment outcomes, including toxicities and patient-reported outcomes, for the different therapies.

Molecular heterogeneity in cancer tumours make it a complex disease to manage and treat. However, there have been significant advancements made in the detection of molecular alterations and we are able to now define distinct disease subtypes which permit targeted selection of therapies, thus optimizing treatment responses for patients and improving their survival.

With CARMA-BROS we will address the objectives that follow.

Primary Objectives:

1. To create a cohort of patients through which to better understand the natural history of disease in Canadian cancer patients with tumours that have been molecularly subtyped and identified to have rare molecular alterations.

2. To compare the natural history, stage distribution, treatment outcomes such as treatment effectiveness (composite of disease progression or death) and treatment toxicities across different patients with different molecular alterations, receiving different lines and types of therapy.

   Secondary Objectives:

3. To determine the incidence, time to development, prevalence, and outcomes of patients with specific patterns of spread, such as brain metastases compared to those without, by different therapies and by molecular alterations.

4. To better understand real-world treatment patterns of rare molecular alterations in the Canadian context, across geographic or other factors, and how treatment patterns evolve over time and as new therapies become available, how patients are investigated and how targeted and other biomarkers are used as part of clinical practice in these patients.

5. To assess quality of life in patients with rare molecular alterations across different stages, lines and types of therapy.

6. To perform exploratory health economic evaluations focused on the costs and benefits of managing patients with rare molecular alterations.

7. To perform biomarker analyses, where appropriate, to improve our understanding of these rare molecular alterations.

Inclusion Criteria:

• Patients ≥ 18 years at cancer diagnosis
• Diagnosed with malignant tumour(s) with molecular testing completed that identified rare molecular alterations
• Accessible/available molecular testing reports/documentation to confirm type(s) of molecular alteration(s) (resulting from the conduct of polymerase chain reaction [PCR] based next generation sequencing [NGS], immunohistochemistry [IHC], fluorescence in situ hybridization [FISH], liquid biopsy)
• Canadian resident received follow-up for cancer care in Canada or is currently receiving/planning follow-up for cancer care to occur in Canada at time of enrollment

Exclusion Criteria:

• Previous refusal of the deceased patient, when living, to enroll in this study or patient approached for this study is unable to provide informed consent

Cancer patients living and deceased who have/had a histologically confirmed rare molecular alteration in their tumours, such as but not limited to ALK, EGFR, ROS1, BRAF, and KRAS G12C from participating sites/cancer centres across Canada.