Challenges in Non-Small Cell Lung Cancer Treatment: Addressing Unmet Needs

EP: 1.Case Overview: A 62-Year-Old Woman with Squamous Histology and PD-L1 Negative mNSCLC

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EP: 2.Challenges in Non-Small Cell Lung Cancer Treatment: Addressing Unmet Needs

EP: 3.PD-L1 Testing and Its Role in Lung Cancer Treatment Decision-Making

EP: 4.Long-Term Immunotherapy Updates in Lung Cancer: Survival Beyond Treatment

EP: 5.Long-Term Benefits of Chemoimmunotherapy in Lung Cancer: Updates and Considerations

EP: 6.Tailoring Lung Cancer Treatment: Balancing Immunotherapy, Chemotherapy, and Targeted Therapies

EP: 7.Bright Future of Lung Cancer Research: Targeted Therapies and Immunotherapy Advancements

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: Despite the great progress that’s been made in molecular medicine and the treatment of non–small cell lung cancer, multiple unmet needs and challenges remain to this day. Specific patient populations that tend to have less benefit from immunotherapy include patients who are PD-L1 negative, those with squamous histology, and those STK11/KEAP1 mutations, which tends to be an adenocarcinoma as opposed to squamous histology as we discussed in the case here. Those patients who have primary refractory disease oftentimes may have PD-L1 low, STK11/KEAP1 biology.

Disease characteristics that remain high risk include patients with leptomeningeal disease who may require whole brain radiation in addition to chemoimmunotherapy, as well as potentially patients with liver metastases. Liver metastases may be potentially immunosuppressive as well. For those patients who progress on chemoimmunotherapy in the front line lacking an actual driver mutation, there are a couple of different treatment options. For those patients with KRAS G12C mutations, these have sotorasib or adagrasib in the second line, [that] represents a reasonable standard of care. Otherwise, typical regimens that are used outside the context of a clinical trial are regimens including docetaxel, docetaxel/ramucirumab, and gemcitabine and other agents that may have potential benefit in the refractory space. But clinical trials remain an important part of addressing these unmet needs, not only for the patient you’re treating in front of you, but also so we can learn how to treat all the patients who’ll be diagnosed with this disease so that we can best improve their outcomes.

Transcript is AI-generated and edited for readability.