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Related Concept Videos

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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Early Detriment Analysis of First-Line Nivolumab plus Ipilimumab-Based Therapy in Patients with Metastatic Non-Small Cell Lung Cancer.

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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3

Luis G Paz-Ares1, Suresh S Ramalingam2, Tudor-Eliade Ciuleanu3

  • 1Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Clinical Research Unit, Universidad Complutense & CiberOnc, Madrid, Spain.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|October 14, 2021
PubMed
Summary

Nivolumab plus ipilimumab demonstrated durable long-term overall survival benefits compared to chemotherapy in previously untreated advanced non-small cell lung cancer (NSCLC). Immune-mediated adverse events were manageable and did not negate the long-term efficacy of this immunotherapy combination.

Keywords:
CTLA-4First-lineImmunotherapyMetastatic non–small cell lung cancerPD-1 checkpoint inhibitor

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Area of Science:

  • Oncology
  • Immunotherapy
  • Clinical Trials

Background:

  • Advanced non-small cell lung cancer (NSCLC) presents a significant therapeutic challenge.
  • Chemotherapy has been a standard first-line treatment, but long-term survival remains limited.
  • Immune checkpoint inhibitors offer a novel approach to cancer treatment by harnessing the patient's immune system.

Purpose of the Study:

  • To evaluate the long-term efficacy and safety of nivolumab plus ipilimumab versus chemotherapy in previously untreated advanced NSCLC.
  • To assess overall survival (OS) as a primary endpoint in patients with programmed death-ligand 1 (PD-L1) expression ≥1% and <1%.
  • To analyze the impact of treatment-related adverse events (TRAEs) on long-term outcomes.

Main Methods:

  • Randomized controlled trial (CheckMate 227) comparing nivolumab plus ipilimumab, nivolumab alone, or chemotherapy.
  • Patients with previously untreated stage IV or recurrent NSCLC were stratified by PD-L1 expression (≥1% or <1%).
  • Efficacy endpoints included OS and safety assessments, with a minimum follow-up of 4 years.

Main Results:

  • Nivolumab plus ipilimumab significantly prolonged OS compared to chemotherapy in both PD-L1 ≥1% (HR=0.76) and PD-L1 <1% (HR=0.64) groups.
  • Four-year OS rates were 29% (PD-L1 ≥1%) and 24% (PD-L1 <1%) with nivolumab plus ipilimumab, versus 18% and 10% with chemotherapy, respectively.
  • Immune-mediated adverse events were generally manageable, occurring early and resolving with treatment; discontinuation due to TRAEs did not impede long-term OS benefits.

Conclusions:

  • First-line nivolumab plus ipilimumab offers durable long-term efficacy in advanced NSCLC patients, irrespective of PD-L1 expression.
  • The safety profile is consistent with prior reports, with manageable immune-related adverse events.
  • Discontinuation of immunotherapy due to TRAEs does not compromise the sustained survival advantage observed in the overall study population.