Perioperative Versus Adjuvant Systemic Therapy in Patients With Resectable Non-Small Cell Lung Cancer - PROSPECT LUNG
Perioperative Versus Adjuvant Systemic Therapy in Patients With Resectable Non-Small Cell Lung Cancer - PROSPECT LUNG
This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To compare the 3-year real-world event-free survival (rwEFS) rate and overall survival (OS) between perioperative and adjuvant immunotherapy-based treatment for patients with resectable non-small cell lung cancer (dual endpoints).
SECONDARY OBJECTIVES:
I. To compare the rates of surgical resection between the two arms. II. To compare the rates of complete resection (R0) between the two arms. III. To summarize and compare rates of adverse events (AEs) resulting in permanent treatment discontinuation, hospitalization, or death between the two arms.
IV. To evaluate the association between locally defined pathological complete response (pCR) and rwEFS in patients randomized to the perioperative arm (arm 2).
V. To compare the rwEFS post 3-years from randomization between the two arms among patients who do not experience an event by 3 years.
EXPLORATORY OBJECTIVES:
I. To compare outcomes according to the systemic therapy administered on each arm.
II. To compare the sites of relapse between the two treatment arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1:
SURGERY: Patients undergo surgery within 28 days of registration.
ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines.
ARM 2:
NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines.
SURGERY: Patients undergo surgery.
ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines.
Patients also undergo computed tomography (CT) throughout the study and may undergo magnetic resonance imaging (MRI) and/or positron emission tomography (PET)/CT at screening.
After completion of study treatment, patients are followed up every 6 months for up to 10 years.
Inclusion Criteria:
Histologically or cytologically confirmed surgically resectable stage IIA to IIIB NSCLC according to the American Joint Committee on Cancer (AJCC) 9th edition (stage IIA to IIIB NSCLC up to single station N2, according to the AJCC 8th edition)
* Note: Patients with resectable stage N2a or T4 are eligible, but patients with stage N2b or N3 are not eligible. Patients with known EGFR or ALK alterations are excluded
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
No prior systemic treatment for NSCLC within 5 years except stage 1 and 2 cancers treated with curative intent
No treatment for another malignancy within 3 years prior to registration, except for stage 1 or 2 cancers treated for curative intent; patients must be disease free for one year prior to registration. Patients with non-melanoma skin cancer, urothelial carcinoma in situ (Tis), noninvasive papillary carcinoma of the urinary bladder (Ta), prostatic intraepithelial neoplasia (PIN), ductal carcinoma in situ (DCIS) of the breast, or cervical intraepithelial neoplasia (CIN) of the uterine cervix are also eligible
No active autoimmune disease, interstitial lung disease, or transplant that precludes safe treatment with immune checkpoint inhibitors
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Jonesboro, Arkansas 72401, United States
Sacramento, California 95817, United States
Baltimore, Maryland 21237, United States
Columbus, Mississippi 39705, United States
New Albany, Mississippi 38652, United States
Lebanon, New Hampshire 03756, United States
New York, New York 10032, United States
Collierville, Tennessee 38017, United States
Silverdale, Washington 98383, United States
Vancouver, Washington 98684, United States
Stevens Point, Wisconsin 54482, United States
Sturgeon Bay, Wisconsin 54235-1495, United States
Summit, Wisconsin 53066, United States