Case Study: Mutation-Negative Patient With Adenocarcinoma

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Moderator, Corey J. Langer, MD, begins a case-based discussion on the treatment of a 46 year-old woman with a history of heavy smoking and a diagnosis of non-squamous, non-small cell lung cancer that is negative for mutations in EGFR, ALK, ROS1, and KRAS.

The patient presented after experiencing dyspnea on exertion and right-sided rib pain, explains Langer. A chest x-ray showed a 3 cm left upper lobe mass, suggesting hilar mediastinal adenopathy. Also, Langer notes, there is a clear lytic lesion in the rib. A CT and PET scan confirms these initial findings and shows areas of osseous metastases. However, an MRI of the brain returned negative.

Unfortunately, Roy S. Herbst, MD, PhD, notes, this patient tested negative for all 4 of the major driver mutations. Given the patient's performance status and age, Herbst feels she is a good candidate for a platinum-based therapy with carboplatin plus pemetrexed. Moreover, with the performance status intact, Herbst may add bevacizumab to the combination, per findings from the PointBreak trial.

When considering a combination it is important to consider toxicity, efficacy, and costs, believes Karen L. Reckamp, MD, MS. In the PointBreak trial, the regimen of carboplatin, paclitaxel, and bevacizumab followed by maintenance bevacizumab had similar outcomes to carboplatin, pemetrexed, plus bevacizumab with maintenance pemetrexed and bevacizumab. However, when considering costs, the addition of both pemetrexed and bevacizumab adds an additional $7,000 per cycle and up to $300,000 depending on the length of maintenance therapy.

As a result of the costs and similar efficacy, if utilizing bevacizumab in this space, Reckamp would opt for the carboplatin, paclitaxel, and bevacizumab regimen followed by maintenance bevacizumab. However, if omitting bevacizumab, Reckamp would administer pemetrexed plus carboplatin with single-agent pemetrexed as maintenance.

In the AVAPERL trial, maintenance therapy with bevacizumab plus pemetrexed demonstrated longer progression-free survival when compared to bevacizumab alone, points out Anne S. Tsao, MD. As a result, it remains unclear whether a combination or a single agent for maintenance therapy is superior. To address this concern, the phase III ECOG 5508 trial is comparing maintenance therapy with pemetrexed alone, bevacizumab alone, or pemetrexed plus bevacizumab following 4 cycles of carboplatin, paclitaxel, plus bevacizumab.   

The AVAPERL trial demonstrated similar findings to other maintenance therapy trials, such as JMEN that showed a survival advantage for single agent pemetrexed, suggests Everett E. Vokes, MD. When considering costs, and the similar efficacy of the combinations, Vokes recommends utilizing carboplatin, paclitaxel, and bevacizumab as an initial treatment followed by single-agent pemetrexed as maintenance.

The JMEN trial had limitations, points out Reckamp. However, when also considering the PARAMOUNT trial it remains clear that pemetrexed is an important maintenance drug. In this trial, single agent pemetrexed maintenance prolonged overall survival. At this point, equivalent data is lacking for maintenance bevacizumab, Reckamp notes.