Durvalumab versus standard chemotherapy drug combination in elderly patients with advanced non‑small cell lung cancer

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What is this study about?

The study focuses on patients with advanced non-small cell lung cancer, a type of lung cancer that has spread beyond the lungs. Two treatment strategies are being compared. One strategy starts with the immune‑boosting drug durvalumab (an immunotherapy) and switches to standard chemotherapy if the disease gets worse. The chemotherapy regimen may include medicines such as vinorelbine, pemetrexed, carboplatin, cisplatin, paclitaxel or gemcitabine, which are given through a vein.

The purpose of the study is to compare how well the two approaches work and how safe they are in older patients whose tumors have a high level of the protein PDL1 or an unknown level. Participants are randomly assigned to receive either the immunotherapy‑first plan or the chemotherapy‑first plan, and the assigned treatment is continued until the disease progresses or side effects become unacceptable, after which the other treatment is started. The study follows patients for at least a year to see how many are alive after 12 months and also records early deaths within four months.

1 randomization

after enrollment, the patient is randomly assigned to one of two treatment arms. the assignment determines whether the first medication is durvalumab (immunotherapy) or a standard chemotherapy regimen.

2 first‑line treatment – durvalumab arm

if assigned to the durvalumab arm, the patient receives durvalumab 1500 mg by intravenous infusion. intravenous means the drug is delivered into a vein through a needle or catheter.

the dose of 1500 mg is given as a single administration each cycle; the exact interval between cycles follows the study protocol (not specified in the source).

treatment continues until disease progression is documented or until the study ends.

3 first‑line treatment – chemotherapy arm

if assigned to the chemotherapy arm, the patient receives a standard chemotherapy regimen that may include one or more of the following drugs at the doses listed:

vinorelbine 30 mg/m² intravenously,

pemetrexed disodium 500 mg/m² intravenously,

carboplatin 450 mg intravenously,

cisplatin 60 mg/m² intravenously,

paclitaxel 90 mg/m² intravenously,

gemcitabine hydrochloride 1200 mg/m² intravenously.

the unit mg/m² (milligram per square meter) adjusts the dose to the patient’s body surface area, which is calculated from height and weight.

each drug is administered by intravenous infusion according to the schedule defined by the study (frequency not specified).

treatment is continued until disease progression is documented or until the study ends.

4 regular monitoring visits

throughout first‑line treatment, the patient attends scheduled clinic visits for physical examination, laboratory tests, and imaging studies to evaluate response and safety.

any side effects are recorded and managed according to standard clinical practice.

5 assessment of disease progression

if imaging or clinical evaluation shows that the cancer has progressed, the patient moves to the second‑line treatment phase as defined by the study.

6 second‑line treatment – switch therapy

patients who received durvalumab as first‑line therapy start the standard chemotherapy regimen described in step 3.

patients who received chemotherapy as first‑line therapy start durvalumab 1500 mg intravenously, following the same administration principles as in step 2.

the same monitoring procedures are applied during second‑line therapy.

7 continued follow‑up

the patient continues to attend regular visits for safety checks, laboratory tests, and imaging until the end of the study period or until further disease progression.

survival status is recorded at 12 months after randomization, and mortality within the first 4 months is specifically noted as a safety outcome.

8 study completion

at the end of the study, all collected data on survival, disease progression, quality of life, and side effects are analyzed to determine the effectiveness and safety of the treatment strategies.

Who Can Join the Study?

Age: You must be 70 years old or older, regardless of gender.
Diagnosis: You need a confirmed diagnosis of primary squamous or non‑squamous non‑small cell lung cancer (a common type of lung cancer).
Cancer stage: Your cancer must be at stage IV or IIIC and have spread to lymph nodes above the collarbone (called supraclavicular nodes).
PD‑L1 level: Your tumor cells must show a PD‑L1 protein expression of 25% or higher, or the test result may be unavailable (only a small number of participants can have an unknown result). PD‑L1 is a protein that helps doctors decide which treatments may work best.
Evidence of disease: There must be a clear sign of cancer on scans or physical exam, with at least one spot that can be measured or not measured.
ECOG performance status: You must have a status of 0 or 1, meaning you are fully active or able to do light work.
Life expectancy: You should be expected to live longer than 3 months.
Kidney and liver health: Your blood tests must show:
- Total bilirubin ≤ 1.5 times the normal upper limit.
- AST and/or ALT ≤ 2.5 times the normal upper limit (or ≤ 5 times if you have liver metastases).
- Serum creatinine ≤ 1.5 times the normal upper limit (or a calculated creatinine clearance of at least 40 mL/min/1.73 m²).
These tests check that your kidneys and liver are working well.
Bone‑marrow health: Your blood counts must be:
- Hemoglobin ≥ 9.0 g/dL (measure of red blood cells).
- Absolute neutrophil count ≥ 1.5 × 10⁹/L (type of white blood cell).
- Platelet count ≥ 100 × 10⁹/L (helps blood clot).
Informed consent: You must sign a written consent form before any study procedures are done.
Patients whose tumors have PD‑L1 ≥ 50% are usually treated with a different standard therapy and are not encouraged to join this study.

Who Cannot Join the Study?

Activating EGFR mutation: having a specific change in the epidermal growth factor receptor gene (such as exon 19 deletion or exon 21 L858R) that can make the cancer grow faster.
ALK or ROS1 positive: test results show the cancer cells have ALK or ROS1 gene changes, identified by special lab techniques (immunohistochemistry or FISH).
Mixed small‑cell lung cancer and NSCLC: the tumor contains both small‑cell lung cancer and non‑small cell lung cancer cells.
Previous chemotherapy or other treatment for advanced lung cancer: you have already received chemotherapy or other medicine for advanced disease (except chemotherapy given more than six months ago as part of earlier surgery).
Prior immunotherapy: you have previously received drugs that affect the immune system, such as anti‑PD‑1, anti‑PD‑L1, or anti‑PD‑L2 antibodies.
Recent use of immunosuppressive medication: you have taken medicines that suppress the immune system within 14 days before the first study dose (low‑dose steroids up to 10 mg prednisone per day are allowed).
Concurrent investigational product: you are currently receiving any other experimental drug or cancer treatment.
Active or recent autoimmune disease: you have an immune‑system disease that was active or diagnosed in the past two years (exceptions are vitiligo, Graves’ disease, or psoriasis that did not need systemic treatment).
Inflammatory bowel disease: you have Crohn’s disease or ulcerative colitis, which are chronic inflammation of the intestines.
History of organ transplant: you have received a donor organ from another person (allogeneic transplant).
Primary immunodeficiency: you have a condition that makes your immune system weak from birth or early life.
Active infections: you have a current infection such as tuberculosis, hepatitis B (positive surface antigen), hepatitis C, or HIV (positive antibody test).
Recent live vaccine: you received a live‑attenuated vaccine (a vaccine containing weakened virus) within 30 days before the first study dose.
Recent other cancers: you have had another cancer in the past five years, except for certain skin cancers, cervical carcinoma in situ, or surgically removed prostate cancer with a normal PSA test.
Brain or spinal cord involvement: you have cancer that has spread to the brain or is compressing the spinal cord, unless it is symptom‑free, previously treated, and you have been off steroids and seizure medicines for at least one month.
Leptomeningeal carcinomatosis: cancer cells are present in the membranes surrounding the brain and spinal cord.
Recent heart attack or unstable chest pain: you have had a myocardial infarction (heart attack) or unstable angina within the past six months.
Significant heart failure: you have congestive heart failure that is New York Heart Association (NYHA) class II or worse.
Uncontrolled high blood pressure: your blood pressure is not adequately controlled with medication.
Serious heart rhythm problems: you need medication for a dangerous heart arrhythmia (except atrial fibrillation or brief fast heart rhythms that are not considered serious).
Severe peripheral vascular disease: you have blood vessel disease in the limbs that is grade 3 or higher, meaning it causes symptoms that limit daily activities and may need surgery.
Prolonged QT interval: your heart’s electrical recovery time (QTc) is 470 milliseconds or longer on an electrocardiogram, indicating a risk of abnormal heart rhythms.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Azienda Ospedaliera Universitaria Federico II Di Napoli	Naples	Italy
Azienda Ospedaliera Universitaria Universita’ Degli Studi Della Campania Luigi Vanvitelli	Naples	Italy

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Ospedale Vito Fazzi Lecce	Lecce	Italy
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania	Catania	Italy
Azienda Sanitaria Locale Viterbo	Viterbo	Italy
IRCCS Ospedale Sacro Cuore Don Calabria	Negrar di Valpolicella	Italy
IRCCS CROB	Rionero In Vulture	Italy
Ospedale Villa Scassi – Sampierdarena-ASL3-Azienda sociosanitaria ligure	Genoa	Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milan	Italy
Ospedale San Raffaele S.r.l.	Milan	Italy
Universita’ Campus Bio-medico Di Roma	Rome	Italy
Universita’ Degli Studi Di Verona	Verona	Italy
Azienda Sociosanitaria Territoriale Santi Paolo E Carlo	Milan	Italy
Azienda USL Toscana Centro	Prato	Italy
Ospedale Fatebenefratelli Isola Tiberina Gemelli Isola	Rome	Italy
Azienda USL Toscana Sud Est	Arezzo	Italy
Azienda Unita Sanitaria Locale Della Romagna	Faenza	Italy
Fondazione Salvatore Maugeri Clinica Del Lavoro E Della Riabilitazione	Pavia	Italy
Centro Di Riferimento Oncologico Di Aviano	Aviano	Italy
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale	Naples	Italy
Casa Sollievo Della Sofferenza	San Giovanni Rotondo	Italy
Azienda Unita Sanitaria Locale Di Modena	Carpi	Italy
Azienda Unita Sanitaria Locale Di Piacenza	Piacenza	Italy
Azienda Sanitaria Universitaria Friuli Centrale	Udine	Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo	Italy
Azienda Unita Locale Socio Sanitaria N 8 Berica	Vicenza	Italy
Ospedale Santa Maria Goretti Latina	Latina	Italy
AORN San Giuseppe Moscati Avellino	Avellino	Italy
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Azienda Ospedaliero-Universitaria Sant’Anna	Ferrara	Italy
Ogbjyyss Gdrtzhbwo	Catania	Italy
Uly Otgujohva Mutwbu &ikcgkj Pgot &tosxjudy Puqlhopzldwduo	Brindisi	Italy
Aflx Sft Pwk	Benevento	Italy
Itfqylzs Rrkbrupkw Ptf Lu Syutjj Dnn Tnzifj Debt Acxycrh Ifbz Sthpoa	Meldola	Italy
Ahrydpx Okzmxgaccyt Nwdoxefid Sg Atrpllz E Bgclwd E C Aloqdg Amrujarukcs	Alexandria	Italy
Acyshsc Udj Iexaw Dn Rgnxhr Eepwst	Reggio Emilia	Italy
Uryivgcoyx Mkfgq Gqrmhtg Ot Cbtndousw	Catanzaro	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not recruiting	20.12.2018

Trial locations

Investigated drugs:

Durvalumab is an immunotherapy drug that helps the body’s immune system see and attack lung cancer cells. In this study it is given through an IV. In the experimental group, patients receive durvalumab as the first treatment. In the standard‑treatment group, patients receive the same drug after their cancer gets worse on chemotherapy.

Vinorelbine is a chemotherapy medicine that stops cancer cells from dividing. It is given by IV and is used as part of the standard chemotherapy regimen in the control arm of the trial.

Pemetrexed is a chemotherapy drug that blocks the enzymes cancer cells need to make new DNA. It is administered intravenously and is included in the standard chemotherapy combinations given to patients in the control group.

Carboplatin is a platinum‑based chemotherapy that damages the DNA of cancer cells, preventing them from growing. It is given by IV and forms part of the standard chemotherapy regimen used in the control arm.

Cisplatin is another platinum‑based chemotherapy that works by harming the DNA of cancer cells. It is delivered intravenously and is one of the chemotherapy agents used in the standard treatment group.

Paclitaxel is a chemotherapy drug that freezes the structures (microtubules) that cancer cells need to split and multiply. It is given through an IV and is included in the standard chemotherapy regimen for the control arm.

Gemcitabine is a chemotherapy medication that looks like a building block of DNA and stops cancer cells from copying their genetic material. It is administered intravenously and is part of the standard chemotherapy regimen used in the control group.

Investigated diseases:

Lung adenocarcinoma

Non‑small cell lung cancer – It is a type of lung cancer that begins in the cells lining the airways. The tumor usually grows slower than small‑cell lung cancer and can spread locally within the lung. In advanced stages, the disease extends beyond the lung to nearby lymph nodes or distant organs. As it progresses, symptoms such as persistent cough, shortness of breath, and weight loss may appear. The cancer cells continue to multiply and invade surrounding tissue over time.

Trial ID:

2024-515326-83-00

Protocol code:

MILES-5

NCT ID:

NCT03975114

Trial Phase:

Therapeutic exploratory (Phase II)

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Durvalumab versus standard chemotherapy drug combination in elderly patients with advanced non‑small cell lung cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?