Treatment Options for Metastatic Large Cell Lung Cancer

Lyudmila Bazhenova, MD:As you can recall, this patient has a low expression of PD-L1. It was only expressed in 2% of the cancer cells, so we have several options. You could consider a platinum-based doublet plus or minus bevacizumab. The drugs of choice could be what this patient received, which were carboplatin, paclitaxel, and bevacizumab. You could consider carboplatin and pemetrexed with or without bevacizumab; there are data for that as well. You could also consider—although I would not recommend it—treatment as per KEYNOTE-021g, which used carboplatin, pemetrexed, and pembrolizumab. What concerns me about this patient and this specific drug selection is the fact that she has active Crohn’s disease. We know from our past literature that if we give immunotherapy to patients with active connective tissue disease, they have about a 60% chance of recurrence of connective tissue disease. The reason to add bevacizumab to carboplatin and paclitaxel stems from the ECOG-4599 clinical trial, which showed that an addition of bevacizumab to carboplatin and paclitaxel improves survival, improves response rates, and improves progression-free survival PFS compared with carboplatin and paclitaxel alone.

In order for patients to be eligible for bevacizumab treatment, there are certain criteria that have to be met. Patients cannot have a current bleeding disorder. It is recommended that patients do not have any history of hemoptysis. Patients cannot have an uncontrolled hypertension. In this specific patient, all of those criteria were met. Therefore, I believe that bevacizumab could have been added to carboplatin and paclitaxel. In my personal experience, bevacizumab is well tolerated. There are certain side effects one needs to be aware of, specifically hypertension, proteinuria, increased incidence of clotting, and increased incidence of bleeding. I believe it is very important to talk to our patients before we initiate bevacizumab to warn them about those side effects, so they can be on the lookout for them as well.

IMpower-150 was a randomized phase III clinical trial for patients with untreated metastatic disease. The study randomized patients into 3 different arms. One arm was carboplatin, paclitaxel, and bevacizumab. The second arm was carboplatin, paclitaxel, and atezolizumab. The third arm was carboplatin, paclitaxel, bevacizumab, and atezolizumab. At this point, the only information we have is a press release saying that IMpower-150 met its primary endpoint, which was progression-free survival, when it compared a quadruplet arm—carboplatin, paclitaxel, bevacizumab, and atezolizumab—to a triplet arm of carboplatin, paclitaxel, and bevacizumab. We do not have any information on the degree of the PFS benefit. We do not have any information on the comparator of carboplatin, paclitaxel, and bevacizumab to the carboplatin, paclitaxel, and atezolizumab arm. At this point, I believe it is too early to make any treatment changes based on IMpower-150 results, but I am looking forward to learning more about the study and understanding what the degree of benefit those patients received is.

Transcript edited for clarity.

• A 70-year old woman presented with persistent cough and congestion lasting more than 6 months
  • She is a non-smoker; drinks alcohol 1-2 times/week
  • PMH: Crohn’s disease managed on infliximab; hypothyroidism, moderately well-managed on levothyroxine; osteoarthritis managed PRN on naproxen
  • Her physical exam and cardiac workup were normal
  • CBC; WNL
  • PS by ECOG assessment is 2
• Chest X-Ray showed mass in the upper right lung
• CT of the chest, abdomen, and pelvis showed a solid 6 X 8 cm. Right-sided pleural mass abutting the apical aspect of the chest wall and 2 small hepatic nodules measuring 1.5 cm and 2 cm.
• Bronchoscopy and biopsy of the lung mass was performed; pathology was consistent with large cell carcinoma
  • Genetic testing was negative for known driver mutations
  • PD-L1 testing by IHC showed expression in 2% of cells
• Brain MRI showed no evidence of CNS disease
• Diagnosis; stage IV NSCLC
• The patient was started on therapy with carboplatin and paclitaxel and bevacizumab