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FDA has approved Opdivo with chemotherapy as neoadjuvant treatment for adult patients with resectable non-small cell lung cancer, regardless of PD-L1 status


The U.S. Food and Drug Administration ( FDA ) has approved Opdivo ( Nivolumab ) 360 mg ( injection for intravenous use ) in combination with Platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable ( tumors 4 cm or more, or node positive ) non-small cell lung cancer ( NSCLC ) in the neoadjuvant setting.

Opdivo plus chemotherapy is approved regardless of PD-L1 status.

The approval is based on the CheckMate -816, the first positive phase 3 trial of an immunotherapy-based combination used before surgery for resectable NSCLC.
The primary endpoints included event-free survival ( EFS ) and pathologic complete response ( pCR ), which were evaluated using independent blinded review, and an additional efficacy outcome measure was overall survival ( OS ). The study compared Nivolumab plus Platinum-doublet chemotherapy ( n=179 ) to Platinum-doublet chemotherapy alone ( n=179 ).

In the trial, when given before surgery, Nivolumab plus chemotherapy has shown a statistically significant improvement in event-free survival with a 37% reduction in the risk of progression, recurrence or death ( hazard ratio [ HR ] 0.63; 95% Confidence Interval [ CI ]: 0.45 to 0.87; P=0.0052 ) compared to chemotherapy alone.
Nivolumab plus chemotherapy has shown a median event-free survival of 31.6 months ( 95% CI: 30.2 to Not Reached [ NR ] ) compared to 20.8 months for patients treated with chemotherapy alone ( 95% CI: 14.0 to 26.7 ).
Additionally, 24% of patients treated with Nivolumab plus chemotherapy achieved pCR ( 95% CI: 18.0 to 31.0 ), compared to 2.2% of patients treated with chemotherapy alone ( 95% CI: 0.6 to 5.6; estimated treatment difference 21.6; 95% CI: 15.1 to 28.2; P less than 0.0001 ).
A prespecified interim analysis for overall survival resulted in a hazard ratio of 0.57 ( 95% CI: 0.38 to 0.87 ), which did not cross the boundary for statistical significance.

CheckMate -816 trial included patients with histologically confirmed Stage IB ( 4 cm or more ), II or IIIA NSCLC ( per the 7th edition American Joint Committee on Cancer / Union for International Cancer Control [ AJCC/UICC ] staging criteria ), ECOG performance status 0 or 1, and measurable disease ( per RECIST version 1.1 ).
Patients with unresectable or metastatic NSCLC, known EGFR mutations or ALK translocations, Grade 2 or greater peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study.
For the primary analysis, 358 patients were randomized to receive either Nivolumab 360 mg plus histology-based Platinum doublet chemotherapy on the same day every three weeks for up to three cycles, or Platinum doublet chemotherapy every three weeks for up to three cycles, followed by surgery.

Adverse reactions leading to the discontinuation of Nivolumab plus Platinum-doublet chemotherapy occurred in 10% of patients and 30% had at least one treatment withheld for an adverse reaction.
Serious adverse reactions occurred in 30% of patients receiving Nivolumab plus Platinum-doublet chemotherapy.
Serious adverse reactions in more than 2% of patients included pneumonia and vomiting.
No fatal adverse reactions occurred in patients who received Opdivo in combination with Platinum-doublet chemotherapy.
The most common ( more than 20% ) adverse reactions were nausea ( 38% ), constipation ( 34% ), fatigue ( 26% ), decreased appetite ( 20% ), and rash ( 20% ).

Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation ( HSCT ); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a Thalidomide analogue and Dexamethasone, which is not recommended outside of controlled clinical trials.

Lung cancer is the leading cause of cancer deaths in the United States. The two main types of lung cancer are non-small cell and small cell.
Non-small cell lung cancer is the most common type of lung cancer and accounts for up to 84% of diagnoses.
Surgery remains the standard of care for resectable NSCLC and while many patients with NSCLC are treated with surgery, between 30% to 55% of patients develop recurrence and die of their disease despite resection. ( Xagena )

Source: BMS ( Bristol Myers Squibb ), 2022

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