Fruquintinib in Patients With Metastatic Colorectal Cancer

The primary objective is to assess the effectiveness of fruquintinib in routine treatment. To this end, the real-world disease control rate will be analyzed, defined as the rate of complete response, partial response, or stable disease, either radiologically documented or clinically assessed by the treating physician.

Further effectiveness objective: Best response radiologically documented or clinically assessed by the treating physician.

Further effectiveness objective: ORR is defined as proportion of patients with any response (partial or complete remission) overall, radiologically documented or clinically assessed by the treating physician.

Further effectiveness objective: TTF is defined as the time from treatment start to discontinuation of treatment for any reason, including progression of disease, treatment toxicity, and death.

Further effectiveness objective: TTNT is defined as the interval from the start of fruquintinib treatment to initiation of the next line of therapy.

Further effectiveness objective: PFS is defined as the time from start of fruiquintinib treatment to disease progression or death from any cause.

Further effectiveness objective: OS is defined as the time from first administration of fruquintinib to death from any cause.

Safety objective: Incidence of (serious) AEs ((S)AEs) as characterized by type, frequency, severity and seriousness.

Safety objective: Incidence of (serious) adverse drug reactions ((S)ADRs) as characterized by type, frequency, severity and seriousness.

Patient-Reported Outcome (PRO) objective: Evaluation of QoL by validated EORTC QLQ-C30 questionnaire during fruquintinib treatment and follow-up period using absolute values over time from baseline to end of study (EOS).

The absolute values over time will be reported on the global health status / quality of life scale, functional scales (physical, role, emotional, cognitive, social) and symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). These scales are scored from 0 to 100. For the global health status/QoL, higher scores represent a higher QoL. For functional scales, higher scores indicate a higher/healthier level of functioning, while for symptom scales lower scores indicate a lower level of symptomatology/problems.

Patient-Reported Outcome (PRO) objective: Evaluation of QoL by validated EORTC QLQ-C30 questionnaire during fruquintinib treatment and follow-up period using changes from baseline over time to end of study (EOS).

The changes from the baseline over time will be reported on the global health status / quality of life scale, functional scales (physical, role, emotional, cognitive, social) and symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). These scales are scored from 0 to 100 and the change is reported as the difference between the scores at baseline and time of interest. For the global health status/QoL and functional scales, positive values indicate an improvement in quality of life while negative values indicate a deterioration in quality of life. For symptom scales, negative values indicate an improvement in symptom burden and positive values indicate an increase in symptom burden.

Patient-Reported Outcome (PRO) objective: Evaluation of QoL by validated EORTC QLQ-C30 questionnaire during fruquintinib treatment and follow-up period using the time to definitive deterioration (TTD).

The time to definitive deterioration will be reported on the global health status / quality of life scale, functional scales (physical, role, emotional, cognitive, social) and symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). These scales are scored from 0 to 100 and the TTD is reported as the period of time until definitive deterioration for each scale.

Assessment of physicians' treatment decision making using the frequency of distinct parameters affecting therapy choice.

Treatment reality objective: Duration of treatment with fruquintinib

Treatment reality objective: Frequency of treatment modifications (treatment interruptions and dose reductions) with reasons, as well as duration of treatment interruptions and number of missed doses.

Treatment reality objective: Frequency of previous therapies (radiation, surgery, systemic with setting: adjuvant/ neoadjuvant/ palliative) and substances for prior systemic antineoplastic therapies.

Treatment reality objective: Frequency of subsequent antineoplastic therapies including substances.

Treatment reality objective: Duration of first subsequent antineoplastic therapy after discontinuation of fruquintinib treatment.

Medical resource utilization objective: Frequency of hospitalizations (planned and unplanned) and emergency unit visits during fruquintinib treatment.

Medical resource utilization objective: Duration of hospitalization during fruquintinib treatment.

For patients with ECOG <2 at inclusion, the time to deterioration to ECOG performance status >/= 2 will be analysed.

Descriptive analysis of disease characteristics, including date of initial diagnosis, stage of initial diagnosis, date of diagnosis of advanced disease, and time from initial diagnosis to diagnosis of metastatic disease for patients with M0-Status at first diagnosis.

Correlation of effectiveness outcomes (DCR, PFS, OS) with relevant genetic alterations (e.g., with a prevalence of >5%)

Identification of ctDNA+ and ctDNA- status Frequency of mutated alleles in ctDNA+ patients Correlation of ctDNA+ and ctDNA- status with effectiveness outcomes (DCR, PFS, OS).

Odds ratio for risk of progression based on ctDNA+ and ctDNA- status