Episode 032: Lung Cancer Series, Pt. 9: Metastatic NSCLC without driver mutations

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we start our discussion on metastatic non-small cell lung cancer, focusing on NSCLC without driver mutations.

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• The approach to treatment of a patient with widespread metastatic NSCLC (mNSCLC) is very different than a patient without distant disease, which highlights why we do what we do:

  • Important to complete staging (discussed in prior episodes) to determine the extent of disease

  • Important to check molecular testing (looking for mutations in the cancer cells) and IHC for tumor proportion score (TPS) helps determine treatment options

• Choosing a treatment is based on:

  • Histology - cannot use pemetrexed or bevacizumab in squamous cell

  • Platinum - Carboplatin is usually used (as opposed to our prior discussions about using Cisplatin because of LACE pooled analysis data)

    • Why is Cisplatin not a great idea? Cisplatin should not be used if patients have (high yield to know cisplatin eligibility criteria!!):

      • Poor performance status

      • Patients with eGFR <60

      • If a patient has baseline hearing loss

      • If a patient has baseline neuropathy

      • Patients with NYHF class III+

    • If patient is getting “palliative” / non-curative setting, you want to spare patients these terrible potential side effects

  • Immunotherapy - All patients with mNSCLC should have IO considered for treatment, unless they have contraindications. Considerations include:

    • Patients with EGFR and ALK mutations - patients with these mutations do NOT respond well to IO so should not use

    • TPS score:

      • Patients with score >50% can get IO monotherapy (spared chemotherapy)

        • KEYNOTE 024: approval for pembrolizumab monotherapy in patient with PDL1>50%

          • Study compared pembro to platinum doublet

          • OS 70% vs. 50% at one year

        • IMPOWER110: approval for atezolizumab monotherapy

          • Study compared atezo to chemotherapy

          • OS 64.9% vs 50% at 12 months

      • Patients with score <50% can get IO + chemotherapy

        • KEYNOTE 189: Showed that the addition of Pembrolizumab to carboplatin/pemetrexed followed by pembro/pemetrexed maintenance in mNSCLC with adenocarcinoma histology had impressive benefits

          • Carbo/taxol/pembro for squamous histology

        • Lots of other trials, check out NCCN for a comprehensive list

    • Putting this all together:

      • In PDL1 >50% WITHOUT SYMPTOMS: IO alone

      • In PDL1 >50% WITH SYMPTOMS: Chemo + IO

      • In PDL1 <50%: 

        • Lots of options, but usually some combination of chemotherapy + IO

        • Many people use Pembro, as it was first to market

• Management of mNSCLC to the brain:

  • Recommend discussion with radiation oncology about role of SRS

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