Advanced-Stage Non-Driver NSCLC: Maintenance Therapy

Benjamin P. Levy, MD:When using an antiangiogenic drug with a platinum doublet, I think what we’ve learned from both the ECOG 4599 and REVEL trials is that when we add these drugs to a platinum doublet, it enhances the response. The response rates from some data with a platinum doublet can be as high as 35% or 40%. When you have response rates like that, I think it’s important that we consider using these drugs.

Maintenance therapy is so important for our patients with advanced-stage non—small cell lung cancer, particularly nonsquamous non–small cell lung cancer. For a patient in which I started on carboplatin/pemetrexed/bevacizumab, if they are a) tolerating the regimen and b) deriving a benefit as evidenced by scans, this is a patient who I would put on maintenance. I would put them on both maintenance pemetrexed and maintenance bevacizumab together every 3 weeks, and that’s important. The discussion about maintenance must start at the beginning of therapy. We cannot have this discussion after 4 to 6 cycles.

So, for patients who come in—in which I’m considering a platinum doublet with or without bevacizumab—I have that discussion up front. I tell them, “You’re going to get 4 to 6 cycles. When we’re done, we’re going to drop one of the drugs, the carboplatin, and we’re going to continue the pemetrexed and the bevacizumab.” Maintenance works, maintenance improves survival, and most often, it’s tolerated. And when you have that, it’s important to deliver it. I don’t want patients to get confused, so I talk about this whole strategy up front. We’ve got very good data, even going back from ECOG 4599, which incorporated a maintenance strategy with bevacizumab, as well as data with pemetrexed, with the PARAMOUNT data showing that maintaining these drugs improves survival. So, I think survival is hard to come by in lung cancer trials, and when we see it, we need to incorporate that strategy that was exploited from the trial.

I usually give maintenance therapy for as long as a) the patient is tolerating it and b) the tumor is in check. Sometimes that could be months, it could be years for patients. I have several patients who have been on maintenance Alimta (pemetrexed) or maintenance Avastin (bevacizumab) for 2 or 3 years. Now, those are certainly outliers, but I generally try to give the drug every 3 weeks or both drugs, Alimta and Avastin, every 3 weeks for as long as they’re tolerating it, as long as their quality of life is maintained, and as long as the tumor is in check.

When patients’ tumors start to grow, I think we have to be very critical in our analysis of what we’re going to do next. We need to think about symptom burden, we need to think about how quickly the tumor is growing. But, importantly, we also need to look at the patient’s performance status. Those all have to go into an individualized treatment decision. I would say, for the most part, if a patient is progressing on maintenance or their tumor is growing on maintenance, this is an opportunity, of course, for a clinical trial if they’re not a part of one initially. At my institution, we certainly try to screen every patient for a second-line clinical trial. But outside of a clinical trial, I would say immunotherapy is very appropriate in this setting. I wouldn’t generally give docetaxel/ramucirumab as a second-line here. This is a patient who has garnered a long benefit from chemotherapy. This is an opportunity for immunotherapy or immunotherapy combinations under the auspices of a clinical trial.

Transcript edited for clarity.

• A 55-year old female presented with chronic cough and 10-lb weight loss
• PMH: never smoker; no family history of cancer; no known exposure to chemicals or asbestos
• Chest x-ray showed a 5.0-cm lesion in the left lower lobe with bulky lymphadenopathy
• Chest CT scan confirmed the presence of a lung mass and enlargement of the right hilar lymph node and bilateral mediastinal lymph nodes
• EUS-guided biopsy was performed
• Pathology revealed adenocarcinoma
• Molecular testing:
  • FISH: negative for ALK translocation
  • NGS: negative for EGFR, ROS1, RET, BRAF, KRAS
  • IHC: PD-L1 expression in 0% of cells
• PET/CT imaging showed 18F-FDG uptake in the lung mass, right hilar lymph node, mediastinum, and left adrenal gland
• MRI of the brain was normal
• ECOG PS, 0
• The patient was started on therapy with carboplatin/pemetrexed and bevacizumab
• The regimen was well tolerated
• After 6 cycles, the patient had a good response
• She was continued on bevacizumab
• After 9 months on therapy, the patient developed cough and weight loss
• Follow-up imaging revealed multiple new lesions in the left adrenal gland and new liver metastases
• Patient was started on atezolizumab, planned for 12 months