Bevacizumab in Combination with Doublet Chemotherapy in Stage IV NSCLC

Alexander Drilon, MD:In my mind, age does not equate with fitness. And the geriatrics people have studied this extensively, and it’s really all about evaluating how somebody is fit in terms of their performance status. This emphasizes the basic questions I highlighted earlier: are they able to take care of themselves at home, are they able to function, perform their activities of daily living? And, that, to me, is more predictive of how well or not well somebody’s going to do with systemic therapy. This is a 72-year-old gentleman, but it seems like, despite the fact that he is symptomatic from his cancer with the dyspnea and the cough, he has an excellent performance status, which was graded as an ECOG 0. For him, certainly if he’s not a candidate for immune therapy, I would definitely consider giving him a platinum doublet, potentially with bevacizumab. So, things I would consider for him might be cisplatinum, or carboplatin, or pemetrexed. And, if without any contraindications, adding in bevacizumab. After 4 to 6 cycles, I would then drop the platinum and give him maintenance therapy with pemetrexed and bevacizumab.

It makes a lot of sense to target angiogenesis for lung cancers because they’re highly vascular, as are many solid tumors. The best trial to talk about is the ECOG 4599 trial, which randomized patients in the first-line setting to carboplatin and paclitaxel, a doublet with or without bevacizumab. And in that trial, we saw a benefit to overall survival of about 2 months going from 10 to 12 months. And so, we demonstrated that in the first-line setting that inhibiting angiogenesis with an antibody to the ligand, VEGF, can result in improved outcomes. We have follow-up data now from the REVEL trial with docetaxel, with or without ramucirumab, which is an antibody to the receptor, where we, again, saw an improvement in outcomes when you added an antiangiogenic to chemotherapy. So, there’s this recurrent theme of trying to starve the tumor of its blood vessel supply, and that resulting in substantial benefits in the clinic.

If I would give something like carboplatin for this gentleman—I can go through each of the doses individually. I do something like an AUC 5 pemetrexed at 500 mg/m², and bevacizumab at 15 mg per kilogram. And, again, I would give that for 4 to 6 cycles, granted the patient’s tolerating therapy well, obviously allowing for any dose reductions or modifications and depending on what his numbers look like, and how he’s feeling. And then, I would launch into the maintenance phase, drop the platinum, and give the doublet of pemetrexed and bevacizumab every 3 weeks until progression or issues with tolerability.

For my first-line patients, what I do in terms of follow-up is I try to do a based-line scan as close as possible in the first cycle of chemotherapy. And then, initially, when they’re getting induction therapy with the platinum doublet, with or without an antiangiogenic, I would scan them every 2 cycles. I would obviously see them in clinic every 3 weeks and do comprehensive metabolic panel and CBC to see how the chemotherapy was affecting them. And the maintenance phase, I relax that a little bit. If patients are doing well with therapy with stable disease on their scans and with good tolerability, I might scan every 3 to 4 cycles.

Casee Scenario 1:

Robert P is a 72 year old retired factory worker from Detroit, Michigan.His medical history is notable for hypertension (well-controlled), hyperuricemia, and gout.

In September of 2015, he presents to his PCP with fatigue, progressive dyspnea, and a persistent, nonproductive cough of approximately 1 month’s duration. He is a former smoker and quit approximately 30 years ago.

• Chest X-ray in October 2015 showed a large mass in the upper left lobe and CT scan showed a left malignant pleural effusion and enlargement of the right mediastinal and hilar lymph nodes.
• MRI of the brain was negative for intracranial metastases.
• The patient underwent resection of the primary mass and biopsy of the affected lymph nodes which showed large cell carcinoma.
• His lung cancer was staged as 4; Biopsy of the primary lesion and lymph node metastases were sent for molecular testing and showed no actionable mutations in EGFR or ALK.
• His current performance status is 0.