Quick Start Durvalumab nach Radiochemotherapie bei nichtkleinzelligem Lungenkrebs im Stadium III

Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion

Participants will receive Durvalumab 1500 mg intravenously every two weeks for 60 minutes. Each treatment is called a cycle and lasts for four weeks (or 28 days).

Participants will be asked to answer all 30 items on the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). This patient-reported outcome measure is designed to measure cancer patients' physical, psychological and social functions. The measure can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is approximately 11 minutes (

Participants will be asked to answer all items on the COPD assessment test (8 items) and the patient-reported outcome measures designed to measure respiratory function. The measures can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is less than 5 minutes.

Participants will be asked to answer the modified medical research council dyspnea scale (1 item), and the patient-reported outcome measures designed to measure respiratory function. The measures can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is less than 5 minutes.

Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) or early (days 8-14 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 14 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.

Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 7 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.

Assess the barriers to the very early (1-7 days) initiation of durvalumab using a survey and free text reporting by study personnel and participants. Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.

Assess the barriers to the early (8-14 days) initiation of durvalumab using a survey and free text reporting by study personnel and participants. Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.

The number of participants with adverse events, serious adverse events, and immune-related adverse events (irAEs) within 85 days (i.e., 1-3 cycles) of the first infusion of durvalumab.

The proportion of patients who have immune-mediated pneumonitis (i.e., excluding pneumonitis due to radiation), any grade, and early onset (i.e., within 85 days [1-3 cycles]).

Participants with all-cause any-grade pneumonitis and early onset.

Participants who discontinue Durvalumab at any point due to an adverse event of any cause.

Using Kaplan-Meier life table methods, overall survival is defined as the number of participants alive at 12 months after the first dose of Durvalumab.

Using Kaplan-Meier methods, progression-free survival is defined as the number of participants alive and without disease progression as documented by the treating provider at 12 months after the first dose of Durvalumab.

Best objective response rate (ORR) to Durvalumab is defined by either a complete response (CR) or partial response (PR) as per RECIST 1.1 criteria by investigator assessment and confirmed on at least two sequential imaging studies that are at least four weeks apart.

• Complete Response (CR): Disappearance of all target lesions.
• Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions.

The change in PROs scores from baseline to cycle 4 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.

The QLQ-LC13 includes questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea and site specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. The change in PROs scores from baseline to week 12 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.

The COPD Assessment Test (CAT) is a questionnaire for people with Chronic Obstructive Pulmonary Disease (COPD). It is designed to measure the impact of COPD on a person's life and how this changes over time. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD. The change in PROs scores using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither).

The mMRC (Modified Medical Research Council) Dyspnea Scale is used to assess the degree of baseline functional disability due to dyspnea.The mMRC breathlessness scale ranges from grade 0 to 4 with grade 4 indicating a higher level of respiratory disease severity.

We will examine risk of clinical sleep disorders and whether there is significant change in this score, using a paired sample t-test. The participant will be asked to answer all 7 items on the Insomnia Severity Index (ISI) and 10 items from the Berlin Sleep Questionnaire, a risk assessment for obstructive sleep apnea.

The Insomnia Severity Index (ISI) is a 7-question tool (0-28 scale) that evaluates insomnia severity based on scores: 0-7 (no clinically significant insomnia), 8-14 (subthreshold), 15-21 (moderate clinical), and 22-28 (severe clinical). Scores of 15 or higher are generally considered clinically significant, often warranting further evaluation.

The Berlin Questionnaire assesses the risk of obstructive sleep apnea (OSA) through three categories: snoring, sleepiness, and hypertension/obesity. High Risk if two or more categories are positive. Low risk only one or no categories are positive.