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. * 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 SRSPlease visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google PodcastLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!