1. Signed Written Informed Consent:
- Subjects must have signed and dated an IRB/IEC approved written informed consent
form in accordance with regulatory and institutional guidelines. This must be
obtained before the performance of any protocol related procedures that are not
part of normal subject care.
- Subjects must be willing and able to comply with scheduled visits, treatment
schedule, and laboratory testing
2. Histologically confirmed NSCLC. A cytologically-proven NSCLC is allowed if a cytoblock
has been prepared.
3. Age: 70 to 89 years
4. Performance status ≤1.
5. Stage IIIB or IIIC non irradiable or IV (8th classification TNM, UICC 2015)
6. Measurable disease as defined by RECIST 1.1
7. No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as
primary therapy for advanced or metastatic disease. Previously irradiated lesion must
not be the only measurable site of disease.
8. At least 3 weeks must have elapsed after major surgery or radiation therapy
9. Adequate biological functions:
Creatinine Clearance ≥ 45 mL/min (Cockcroft or MDRD or CKD-epi); neutrophiles ≥
1500/mm3 ; platelets ≥100 000/mm3 ; Hemoglobin ≥ 9g/dL ; hepatic enzymes < 3x ULN
except for patients with hepatic metastases (< 5 x ULN), total bilirubin ≤ 1,5 x ULN
except for patients with proved, Gilbert syndrome (≤ 5 x ULN) or patients with hepatic
metastases (≤ 3,0 mg/dL).
10. Life expectancy of at least 12 weeks
11. For male patients with female partners of childbearing potential, agreement (by
patient and/or partner) to use a highly effective form(s) of contraception that
results in a low failure rate [< 1% per year] when used consistently and correctly,
and to continue its use for 6 months after the last dose of treatment. Male patients
should not donate sperm during this study and for at least 6 months after the last
dose of treatment.
Oral contraception should always be combined with an additional contraceptive method
because of a potential interaction with the treatment. Male patients must always use a
12. Patient covered by a national health insurance
13. Protected adults can participate if they are able to make decision about their medical
treatment according to guardianship judgment.
1. Small cell lung cancer or tumors with mixt histology including a SCLC component
2. Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X
mutations in exon 21, G719A/S mutation in exon 18) or HER2 exon 20 insertion (either
tissue or plasma cfDNA mutation).
3. Known ALK or ROS1 gene rearrangement as assessed by IH, FISH or NGS sequencing
4. Previous or active cancer within the previous 3 years with the exception of those with
a negligible risk of metastasis or death and treated with expected curative outcome
(such as adequately treated carcinoma in situ of the cervix, basal or squamous cell
skin cancer or ductal carcinoma in situ treated surgically with curative intent. For
other type of cancer, please contact IFCT). Patients with a prostate adenocarcinoma
history within the previous 3 years could be included in case of localized prostate
cancer, with good prognostic factors according to d'Amico classification (≤ T2a and
Score de Gleason ≤ 6 and PSA (ng/ml) ≤ 10), provided they were treated in a curative
way (surgery or radiotherapy ± hormonotherapy, without any chemotherapy)
5. Mini Mental Score < 24
6. Previous systemic treatment (including but not limited to chemotherapy, targeted
treatment or immunotherapy) except for adjuvant therapy given more than 5 years ago.
7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
8. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any component of the atezolizumab formulation
9. History of autoimmune disease, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel
disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
vasculitis, or glomerulonephritis Patients with a history of autoimmune-related
hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this
Patients with rheumatoid arthritis without exacerbation during one year and with no
more than 10 mg oral prednisone /day or equivalent may be included after
Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen
are eligible for this study
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
excluded) are permitted provided that they meet the following conditions:
- Rash must cover less than 10% of body surface area (BSA).
- Disease is well controlled at baseline and only requiring low potency topical
- No acute exacerbations of underlying condition within the previous 12 months (not
requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids,
biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
10. Symptomatic brain metastases requiring corticosteroids.
11. Spinal cord compression not definitely treated by surgery and/or radiation therapy or
with neurological sequelae.
12. Leptomeningeal disease
13. Uncontrolled tumor-related pain.
14. Uncontrolled or symptomatic or requiring Denosumab hypercalcemia .
15. Corticosteroids > 10mg oral prednisone/day or equivalent.
16. Immunosuppressive medications within 2 weeks before randomization
17. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans, COPD), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the
radiation field (fibrosis) is permitted.
18. HIV positive serology (test at screening),
19. Patients with active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen HBsAg test at screening) or hepatitis C Patients with past
hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence
of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they
are negative for HBV DNA.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is
negative for HCV RNA.
20. Active tuberculosis
21. Severe infection within 4 weeks before randomization
22. Received therapeutic oral or iv antibiotics within 2 weeks before randomization.
23. Administration of live attenuated vaccine within four weeks before randomization or
anticipation that such a live attenuated vaccine will be required during the study.
24. Serious undergoing diseases or comorbidities precluding the possibility for the
patient to receive the treatments.
25. Polyneuropathy ≥ grade 2 CTC
26. Treatment with an investigational drug during the 4 weeks preceding inclusion in the
27. Known allergy to Cremophor EL