Long-Term Immunotherapy Updates in Lung Cancer: Survival Beyond Treatment

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A concise review of five-year updates from pivotal immunotherapy studies in lung cancer, highlighting the durability of responses and treatment options for high-risk disease

CASE PRESENTATION

62-year-old woman presented to the ED with vague complaints of voice changes and cough.

  • She gave a history of a recent, 11-pound weight loss.

Past Medical, Family, and Social History

  • Hypertension, controlled with ACEi 10 mg PO QD
  • Hyperlipidemia, treated with atorvastatin 20 mg PO QD
  • COPD, treated with maintenance fluticasone furoate, umeclidinium, and vilanterol (100/62.5/25 mcg oral inhalation QD)
  • Mother: deceased at 65 years-of-age from lung cancer
  • Former smoker: 10-15 pack years. Quit tobacco habit 25 years ago.

Physical Examination

  • Current weight: 125 lbs.
  • ECOG PS 1

Diagnostic Workup

  • CT of Thorax: discovered a 4 cm nodule in the left, upper lobe
  • CT of Abdomen reveals metastases to the liver
  • MRI of Brain: negative for brain metastases

Final Pathology: consistent with squamous cell carcinoma; metastatic stage IV

PD-L1 expression by IHC: 0%

NGS: No actionable mutations

Treatment

  • Therapeutic options were reviewed with the patient and family.
  • She was initiated on:
    • Nivolumab 360 mg IV Q3W + ipilimumab 1 mg/kg IV Q6W + 2 cycles of chemotherapy Q3W

Transcript:

Sandip P. Patel, MD: Recently, there have been multiple long-term updates on several pivotal immunotherapy studies in the frontline setting, including KEYNOTE-024 [NCT02142738] in PD-L1–high patients using pembrolizumab. The IMpower110 study [NCT02409342] looking at atezolizumab in PD-L1 high frontline non–small cell lung cancer, the EMPOWER-Lung 1 study [NCT03088540] looking at cemiplimab in PD-L1–high patients, and finally, nivolumab plus ipilimumab vs chemotherapy in the CheckMate 227 study [NCT02477826].

Here we’re starting to see 5-year updates. Many of these regimens were given in a clinical trial for 2 years, and the patients stopped per protocol-directed therapy. Now we’re seeing survival 2, 3 years beyond their last dose of immunotherapy, which makes a lot of sense because technically [with] these immune checkpoint blockade agents, the real drug is the patient’s own immune system. Similar to vaccine, they’re able to get an antitumor response that’s more durable. Across these studies, what we’ve seen is that those patients who tend to make it to the 2-to-3-year mark with nice remissions continue to have a durability of their remissions that last years, which is the tail end of the survival curve, showing that patients off treatment could continue to benefit from agents they received years before.

The approval of single-agent immunotherapy in the context of anti–PD-1– and anti–PD-L1–based approaches vs dual immunotherapy, which feature the addition of an anti–CTLA-4 agent, have revolutionized the treatment of nontargetable driver mutation non–small cell lung cancer. In particular, smoking-related lung cancer has had a dramatic improvement in survival driven by the appropriate use of immunotherapy. The ability to select single-agent immunotherapy vs dual-immune checkpoint blockade, especially for those patients who may have particular benefit from the addition of anti–CTLA-4, remain useful tools in our therapeutic armamentarium as we try to tackle higher-risk disease, potentially.

Transcript is AI-generated and edited for readability.

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