Selecting Immunotherapy for Nondriver Metastatic NSCLC

Mark A. Socinski, MD:In a patient who does not have on oncogenic driver, the standard of care now is chemotherapy, and there are various options. The options vary based upon the histology of the cancer. Options are different in adenocarcinoma than they are in, say, squamous carcinoma. And then with the recent data that we’ve had over the past 3 months, are you going to integrate immunotherapy? And I think we had several trials presented recently. The 2 prominent ones are KEYNOTE-189 and IMpower150, which took the 2 FDA approved chemotherapy platforms. In KEYNOTE-189, it was carboplatin and pemetrexed. In IMpower150, it was the platform of carboplatin-paclitaxel-bevacizumab. Again, 2 FDA [US Food and Drug Administration]-approved regimens, and grafted on to them in a phase III setting, immunotherapy. In the case of KEYNOTE-189, it was pembrolizumab. In the case of IMpower150, it was atezolizumab. Both of those trials showed significant benefit in overall survival, progression-free survival, overall response rates, and durability of response. So, these are 2 positive trials saying that whatever platform you’re using—carboplatin-pemetrexed or carboplatin-paclitaxel-bevacizumab—the incorporation of immunotherapy in those regimens actually improves outcomes.

Now this gentleman, because of the history of intermittent hemoptysis, would not have been a candidate for bevacizumab because that’s an absolute or relative contraindication to the use of that drug because of the risk of pulmonary hemorrhage. But he was a perfectly appropriate candidate for the chemotherapy platform of carboplatin/pemetrexed. He had no contraindications to immunotherapy. So, in my opinion, he received the standard of care, state of the art to treatment recommendation, combining immunotherapy with that carboplatin-based doublet.

When I initially discuss patient treatment options with a patient with stage IV disease, I say that there are really 3 buckets of options. One is targeted therapies, but in those patients with targeted therapies, you have to have a target. And we evaluate patients for the targets ofEGFRmutations,BRAFmutations,ALKandROS1translocations, and there are otherRETtranslocations,METamplification or exon 413, skip mutations,HER2alterations,NTRKalterations. There are a growing number of actionable oncogenetic drivers that we treat—if you have a target, you use targeted therapy. So, that’s 1 bin.

The second bin is, which patients may you treat with immunotherapy alone? And right now, in my practice in those who had very high staining for PD-L1 [programmed-cell death ligand 1], which is greater than 50%, I will use pembrolizumab as a single agent in the vast majority of those patients. In the remaining bin, we have patients who are appropriately treated with chemotherapy, and based upon, as I previously said, KEYNOTE 189 and IMpower150, I now think that combining immunotherapy with those chemotherapy platforms is the appropriate treatment strategy at this point.

This gentleman had adenocarcinoma and so carboplatin-pemetrexed as well as carboplatin-paclitaxel-bevacizumab are 2 FDA-approved standards for the treatment of adenocarcinoma. Let’s say he had squamous carcinoma. We had another trial, KEYNOTE-407, as well as IMpower131, that showed they were both positive showing the benefit of adding immunotherapy to a platinum taxane therapy in squamous histology patients. So, both in squamous and nonsquamous we have integrated immunotherapy with our standard chemotherapy regimens based on overall survival benefit.

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