Beyond Frontline Treatment of Nondriver mNSCLC

Mark A. Socinski, MD:Hopefully, this patient would be on the KEYNOTE-189 regimen for a very long time. But we don’t think that the regimen cures patients of their stage IV cancer. That may happen in a small number of patients. But for the most part, we would anticipate that our patient for discussion today at some point would exhibit disease progression. Presumably if he was on pembrolizumab for a long period of time, I would think about, depending on upon how long he was, the options would be categorized as follows.

The standard option, kind of the textbook option, would be to go to what I would call the standard second-line treatment, which would be docetaxel with or without ramucirumab. Typically, I do use ramucirumab. We have phase III data from the REVEL trial that show that the combination is better than docetaxel alone. That’s probably the most common thing I do.

Now some thinking out of the box options would be, maybe would you add chemotherapy back into the mix with pembrolizumab for 2 to 3 cycles to see if you could reinduce a response? We don’t have any rationale for that at this point. If you have gone for, say, more than a year before you’ve had chemotherapy, there is precedent that you know many tumors where you can see repeat sensitivity to that, so that would be an option, although I must say, we don’t have any clinical data to date.

We also know that there’s a little bit of a fuzzy area in terms of continuing immunotherapy past progression. And that has a lot of nuance to it. There are some people who I would try to hang on immunotherapy for a while. There are others who I clearly would switch to, say, docetaxel-ramucirumab. It would have to do with the bulk of their disease—how quickly were they progressing, how symptomatic were they, and these sorts of things. If they were progressing rapidly, they had bulky disease, they are very symptomatic, I think you have to abandon the approach of immunotherapy and go back to chemotherapy, and typically I would use docetaxel-ramucirumab.

Again, I would think about going back to say carboplatin/pemetrexed if it had been more than a year, although I have to admit it’s a relatively data-free zone, if you will. There are not a lot of data in that setting to give us really good guidelines.

Between AACR [American Association for Cancer Research Annual Meeting] and ASCO [American Society of Clinical Oncology Annual Meeting] this year, we had a titanic shift in the standard of care. Trials such as KEYNOTE-189, IMPower150, KEYNOTE-407, and IMPower131 in squamous really changed the standard of care. Essentially, what we’ve done is taken the chemotherapy, which we used to do in the first-line setting, and immunotherapy, which was the standard second-line approach, and we’ve combined them. And by combining them, we have improved outcomes both in nonsquamous as well as squamous. So, I think this is wonderful news for patients. And we’ve done that without substantially putting patients at risk of significant toxicities. We have to be aware of the adverse effects, but these regimens combined have very nice tolerability profiles and the toxicity is certainly not prohibitive. So, it’s a new dawn of using immunotherapy, sometimes alone, sometimes with chemotherapy, that really improves outcomes for patients with advanced non—small cell lung cancer.

Transcript edited for clarity.

A 66-Year-Old Man With NSCLC

May 2018: H&P

• A 66-year-old man presented to primary care with complaints of persistent cough and shortness of breath with easy exertion.
  • PE: Average height, very thin (BMI = 18 kg/m²); says he has been losing weight although not dieting; mild fever (100.6 degrees); intermittent hemoptysis
  • Lab results: CrCL 75 mL/min; A1C 6.8%; WBC 15K/µL
  • PMH: HTN managed on atenolol; former smoker (30 pack-years); attributes cough to smoking but has persisted for 3 years now since he quit
• Primary care suspected bronchitis and prescribed amoxicillin; referred to pulmonology

June 2018: Pulmonology evaluation

• Pulmonologist evaluated patient for COPD: diminished lung function on spirometry
• CT revealed a 3-cm mass in left lung and multiple (<2 cm) masses in right lung, pleura, and axial lymph nodes; patient referred to oncology.

July 2018: Oncology exam

• Biopsy identified adenocarcinoma in left lung with lymph node and pleural involvement
• Molecular testing:
  • ALK& ROS1 rearrangement, negative
  • EGFR, KRAS wild-type
  • KRAS negative
  • PD-L1 TPS: 45%
• Additional testing: Abdominal CT, NED; Brain MRI, NED
• Diagnosis: Stage IVA lung adenocarcinoma without molecular drivers

August 2018

• Patient begins treatment with pemetrexed/carboplatin plus pembrolizumab 200 mg q3 wks