Nondriver NSCLC: Treating Patients Second-Line and Beyond

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Anne Tsao, MD:In patients who’ve received a triplet regimen for metastatic adenocarcinoma of the lung, such as carboplatin/pemetrexed and pembrolizumab, when they develop progression, you have to use your best judgment. It’s unclear whether sequencing these immunotherapies will benefit the patients. But certainly, in the salvage setting, they are included: regimens such as nivolumab, ipilimumab/nivolumab, and docetaxel/ramucirumab. There’s also gemcitabine and vinorelbine, and there is also afatinib. You have to use your best judgment. We do not have enough data yet to know whether sequencing immunotherapies will be beneficial for patients and whether it will prolong survival. But there are certainly huge efforts under way right now in lung cancer to determine whether this is safe and whether it’s efficacious.

In this patient, if she maintains her performance status after the triplet regimen, I certainly would consider rechallenging her with an immunotherapy if she appeared to gain significant benefit from the triplet regimen. For instance, if she is on maintenance therapy beyond a year, I certainly would consider continuing immunotherapy in the absence of clinical trial data. If, however, she developed an immune-related adverse event or her performance status were compromised a little bit from this, you certainly could consider using gemcitabine. We could also consider using docetaxel with or without ramucirumab. These are all options for this patient.

The field is very promising right now, and it’s a very exciting time. We have had so many new therapies and new indications for all these new drugs: immunotherapies as well as targeted agents. The field is moving so quickly now that I tell all our patients, “We just need to make this a chronic disease for you, keep you doing well with a good performance status, and keep your cancer contained until the next new treatment makes it to the market.”

Transcript edited for clarity.


A 64-Year-Old Woman With Metastatic NSCLC

  • A 64-year-old woman reported having cough and shortness of breath on exertion for the past 2 years, but now having persistent symptoms even without exertion.
    • PE: revealed diminished breath sounds and minimal expiratory wheezing in right lung; not physically fit
    • PMH: mild hypertension well managed on lisinopril
    • SH: smoker, 15 pack-years
  • CT scan revealed 2 masses in RUL and several small masses in the liver
  • Biopsy of right lung mass confirmed grade 2 adenocarcinoma
    • EGFRnegative,KRASnegative
    • IHC negative forALK-rearrangement,ROS1-rearrangement
    • PD-L1 TPS: 56%
  • PET scan showed multiple areas of FDG uptake in liver, SUVmax, 7.8
  • Brain MRI, negative for metastases
  • Diagnosis: stage IV lung adenocarcinoma
  • Patient started on treatment with pembrolizumab/pemetrexed/carboplatin
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