Case study 77.1

A 64-year-old man, with a 40-pack-year history, presents with chest pain and dyspnea. During his work-up, a chest X-ray reveals a right lower lobe mass. He undergoes a bronchoscopy and biopsy that reveals non-small-cell lung cancer (NSCLC), adenocarcinoma histology. Computed tomography (CT) and positron emission tomography (PET) scans reveal a right lower lobe mass, mediastinal and hilar adenopathy, and hepatic metastases. Magnetic resonance imaging (MRI) of the brain is negative for metastases.

1. What molecular testing on his cancer is appropriate for this patient?

Epidermal growth factor receptor (EGFR) mutation
K-ras mutation
EML4–ALK translocation
ROS1 translocation
All of the above

EGFR mutations are found in 15% of patients, EML4–ALK translocations are found in 4–5% of patients, and ROS1 translocations are found in 1–2% of patients. K-ras mutations are found in 20–25% of patients and may be associated with a poorer prognosis. As new molecular (genomic or proteomic) tests are available, the relevance of other molecular diagnostic tests will expand. There are a number of companies (as well as academic sites) that offer these tests, and it is important to have expert analysis of these markers.

2. This patient tests negative for an EGFR mutation and for EML4–ALK and ROS1 translocations. What would be an appropriate initial treatment regimen?

Carboplatin, paclitaxel, and bevacizumab
Cisplatin and pemetrexed
Carboplatin and paclitaxel
Cisplatin and gemcitabine
A and B
All of the above

All of the above regimens are appropriate for this patient, but A is a regimen that should be used as long as patients do not have a contraindication for use of bevacizumab. Eastern Cooperative Oncology Group (ECOG) trial E459 randomized patients to carboplatin and paclitaxel versus the same chemotherapy with bevacizumab, followed by maintenance therapy with bevacizumab until disease progression. The data revealed a significant increase in median overall survival, progression-free survival, objective response, and 1- and 2-year survivals in the group that received bevacizumab. However, in clinical practice, decision making has to be based on how the patient can tolerate the therapy.

3. After completing 4–6 cycles, this patient has a partial response to therapy. Which of the following would be the best options for this patient?

Maintenance therapy with single-agent bevacizumab
Maintenance therapy with pemetrexed
No further therapy, but restart therapy when he progresses.
All of the above

If the patient is started on carboplatin, paclitaxel, and bevacizumab, then bevacizumab should be continued after an initial 4–6 cycles until disease progression as it has shown superior efficacy in ECOG trial E459. If the patient were started on cisplatin and pemetrexed, then pemetrexed should be continued after an initial 4–6 cycles until disease progression.