Impact of eHealth Monitoring on Overall Survival in Patients With Metastatic NSCLC / Extensive-stage SCLC / Advanced TNBC Under First-line Treatment With Atezolizumab Plus Chemotherapy

Study Overview
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Brief Summary
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The current study is aimed to test the benefit of a web-based application tool in NSCLC, SCLC and TNBC patients during the recently approved first-line treatment strategy with atezolizumab in combination with chemotherapy.

Detailed Description
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Checkpoint inhibitors represent new, promising treatment opportunities in the palliative lung cancer setting. Among programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, atezolizumab (Tecentriq® ), a PD-L1 inhibitor, has been shown to ameliorate outcomes for NSCLC patients with metastatic disease: The open-label phase II multicenter studies POPLAR and BIRCH revealed an improved overall response rate and a benefit in overall survival (OS) under atezolizumab monotherapy. The open-label, randomized phase III OAK trial led to atezolizumab approval as monotherapy for patients with metastatic NSCLC whose disease progressed during or following platinumcontaining chemotherapy regardless of PD-L1 status. Despite these developments, platinum-based chemotherapy regimens are still standard of care for lung cancer without druggable alterations. Lately combining conventional chemotherapeutics with immunotherapy showed promising results: A phase I study of first-line atezolizumab plus chemotherapy demonstrated efficacy regardless of PD-L1 status and an acceptable safety profile in multiple tumor types. Accordingly, ongoing phase III trials address potential benefits of platinum-based immunotherapy combinations in comparison to standard platinum-containing regimens in first-line NSCLC and SCLC. If additional bevacizumab might further enhance atezolizumab efficacy by inhibiting vascular Endothelial Growth Factor (VEGF)-related immunosuppression is currently investigated in the IMpower150 trial. Patients under intensive care for advanced cancers develop symptoms due to cancer progression and, possibly, due to therapy-related sideeffects. These symptoms are often not detected promptly by the treating physician leading to functional impairment and deconditioning of the patient's status with potential implications for the general outcome. Improved symptom control in late-stage cancer under exhaustive therapy regimens was achieved through intensified symptom management. Systematic collection of symptom information by electronic patientreported outcomes (ePROs) in addition to clinical routine provides an attractive basis for intensified symptom management. However, despite new, intriguing results, the proof of a significant benefit (defined as primary outcome measure) under first-line treatment is still limited in oncology trials. In the palliative setting of lung cancer, routine treatment monitoring includes imaging at certain intervals. However, as approaching imaging assessments clarify the patient's fate, they are often a source for anxiety and concern. Additionally, patients with emerging symptoms often wait until the next routinely scheduled consultation with their treating oncologist. As a consequence, tumor progression without therapeutic hindrance over several weeks may occur and naturally shorten the patient's survival time. Clinical monitoring via self-assessed symptom-based approaches endows several benefits. Remarkably, 75-95% of relapses in lung cancer patients come with symptoms and, thus, a direct PRO measurement might be useful in the detection of an early disease progression. Easily accessible web-based application tools such as CANKADO were developed to report PROs more frequently compared to routine assessment. These tools help to strengthen the connection between patient and treating physician and to reduce patients' anxiety. Of note, even during treatment with toxic chemotherapy, most patients are willing and able to self-report via the web. Physicians appreciate PROs and trust in patient-reported information. In line with this, several promising studies confirmed a benefit from proactive, web-based monitoring programs. If symptoms occurred or worsened, the respective physician was informed earlier what resulted n improved OS, quality of life (QoL) and also in economic advantages due to less unnecessary routine check-ups. So far, these studies were performed on heterogeneous patient populations during chemotherapy. The current study is aimed to test the benefit of a web-based application tool in NSCLC, SCLC and TNBC patients during the recently approved first-line treatment strategy with atezolizumab in combination with chemotherapy.

Official Title
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Multicenter Study to Evaluate the Impact of eHealth Monitoring on Overall Survival in Patients With Metastatic Non-squamous NSCLC or Extensive-stage SCLC or Advanced TNBC Under First-line Treatment With Atezolizumab in Combination With Chemotherapy

Conditions
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Stage IV Non-small Cell Lung Cancer, Extensive-stage Small Cell Lung Cancer, Advanced (Locally Advanced and Inoperable or Metastatic), PD-L1 IC-positive TNBC

Intervention / Treatment
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* Other: eHealth system support for symptom management via CANKADO


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histologically or cytologically confirmed stage IV non-squamous NSCLC or histologically or cytologically confirmed extensive-stage SCLC or histologically or cytologically confirmed advanced (locally advanced and inoperable or metastatic), PD-L1 IC-positive TNBC, respectively Indication and decision for approved therapy with atezolizumab and bevacizumab in combination with carboplatin and paclitaxel induction followed by atezolizumab/bevacizumab maintenance therapy in accordance with the current German SmPC of atezolizumab for first-line treatment of stage IV non-squamous NSCLC atezolizumab in combination with carboplatin and nab-paclitaxel induction followed by atezolizumab maintenance therapy in accordance to the current German SmPC of atezolizumab for first-line treatment of stage IV non-squamous NSCLC atezolizumab in combination with carboplatin and etoposide induction followed by atezolizumab maintenance therapy in accordance to the current German SmPC of atezolizumab for first-line treatment of extensive-stage SCLC atezolizumab in combination with nab-paclitaxel in accordance to the current German SmPC of atezolizumab for treatment of advanced, PD-L1 IC-positive TNBC Aged ≥ 18 years ECOG 0-2 In possession of a web-connected, frequently used, electronic device (smartphone, tablet, PC) Willingness and ability to participate at the paper-based or digital questionnaire project and to participate at an initial training and to regularly use the web-based application tool CANKADO Fluent in written and spoken German Written (signed and dated) informed consent Exclusion Criteria: Prior treatment for stage IV non-squamous NSCLC (prior TKI therapy is allowed for EGFR mutant or ALK-positive NSCLC) or prior systemic treatment for extensive-stage SCLC or prior systemic chemotherapy for advanced TNBC History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CANKADO (Arm A)<br>CANKADO application as eHealth support system: Patients use CANKADO for regular symptom self-reporting in addition to standard of care symptom management. | Other: eHealth system support for symptom management via CANKADO<br>* Regular use of eHealth support system CANKADO by the patient: symptom self-reporting triggering alerts to the patient; in addition to standard of care symptom management.<br>|
| Control (Arm B)<br>Control arm without eHealth support: Patients recieve standard of care symptom management. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time from randomization to death from any cause. Patients not experiencing an event (i.e., patients alive at their individual end of study) will be censored with the last date the patient was known to be alive. | 72 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response | The best documented response (in terms of complete response [CR], partial response [PR], stable disease [SD], or progressive disease [PD]) per patient, as assessed by the treating physician. | 72 months | 
| Overall response rate (ORR) | The proportion of patients showing a best overall response of CR or PR (as assessed by the treating physician). | 72 months | 
| Disease control rate (DCR) | The proportion of patients showing a best overall response of CR, PR, or SD (as assessed by the treating physician). | 72 months | 
| Progression Free Survival (PFS) | The time from randomization to tumor progression or death from any cause, whatever occurs first. Patients being event-free (i.e., alive and progression-free) by the time of analysis or starting a new antineoplastic therapy before progression, will be censored at the date of the last adequate tumor assessment. | 72 months | 
| Change from baseline in the global health scale score | To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Change from baseline in the global health scale score | 72 months | 
| Change from baseline in the functional/symptom scores | To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Change from baseline in the functional/symptom scores | 72 months | 
| Time to deterioration in global health scale score | To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Time to deterioration (TTD) by ≥ 10 points in the global health scale score | 72 months | 
| Time to deterioration in functional/symptom scores | To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Time to deterioration (TTD) by ≥ 10 points in the functional/symptom scores | 72 months | 
| Alerts | Frequency and total number of eHealth Support system (EHSS) alerts. | 72 months | 
| Sensitivity of alerts | Ratio of alert-initiated visits that result in detection of tumor progression and/or action-requiring symptom management (as evaluated by the oncologist) and all visits which result in detection of tumor progression and/or action-requiring symptom management. | 72 months | 
| Specifity of alerts | Ratio of non-alert-initiated visits with neither detected tumor progression nor action-requiring symptom management (as evaluated by the oncologist) and all visits with neither detected tumor progression nor action-requiring symptom management. | 72 months | 
| Positive predictive value of alerts | Ratio of alert-initiated visits that resulted in detection of tumor progression and/or action-requiring symptom management and all alert-initiated visits. | 72 months | 
| Negative predictive value of alerts | Ratio of non-alert-initiated visits with no result (i.e., neither detected tumor progression nor action-requiring symptom management) and all non-alert-initiated visits. | 72 months | 
| Progression-detection rate | The proportion of individuals who test positive for a first tumor progression during atezolizumab therapy in a specific type of tumor assessment (i.e., alert-triggered vs. non-alert-triggered), compared to the total number of first detected progressions during atezolizumab therapy (i.e., progressions detected in all tumor assessments during scheduled as well as unscheduled visits). | 72 months | 
| Patient compliance | Intensity of use of application tool (defined as number of utilizations per week over the total observation time). | 72 months | 
| Safety and tolerability | Frequency and severity of (serious) adverse events ((S)AEs) coded by the Medical Dictionary for Regulatory Activities (MedDRA), summarized by Preferred Term and System Organ Class and graded according to CTCAE v5.0. Frequency and severity of (serious) adverse drug reactions ((S)ADRs) with causal relationship to bevacizumab and/or atezolizumab coded by the MedDRA, summarized by Preferred Term and System Organ Class and graded according to CTCAE v5.0. | 72 months | 
| Treatment duration of first-line atezolizumab | Treatment duration of first-line atezolizumab (including maintenance therapy) | 72 months | 
| Relative dose intensity of first-line atezolizumab | Relative dose intensity of first-line atezolizumab (including maintenance therapy) | 72 months | 
| Treatment duration of each combined first-line antineoplastic therapy substance | Treatment duration of each combined first-line antineoplastic therapy substance | 72 months | 
| Relative dose intensity of each combined first-line antineoplastic therapy substance | Relative dose intensity of each combined first-line antineoplastic therapy substance | 72 months | 
| Treatment duration of combined first-line bevacizumab | Treatment duration of combined first-line bevacizumab (including maintenance therapy) | 72 months | 
| Treatment modifications of first-line atezolizumab and all combined antineoplastic substances | Therapy details and subsequent therapy lines based on Treatment modifications of first-line atezolizumab and all combined antineoplastic substances | 72 months | 
| Subsequent antineoplastic therapy lines | Therapy details and subsequent antineoplastic therapy lines | 72 months | 
| Subscale scores and single item responses | To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms Subscale scores and single item responses in Patient Reported Outcomes on QoL in both arms | 72 months |