You are here: Home: LCU 3 | 2006 : Edward S Kim, MD

Tracks 1-19

Track 1 Introduction Track 2 MD Anderson trial of carboplatin/ docetaxel and bevacizumab as first-line therapy for NSCLC Track 3 Safety and efficacy of different taxanes with bevacizumab Track 4 Future directions in the management of lung cancer Track 5 Importance of tissue acquisition in clinical research Track 6 Case discussion: A 52-year-old woman with NSCLC metastasized to the brain Track 7 Potential role of predictors of response to select therapy Track 8 Risk and morbidity associated with tissue acquisition Track 9 Ongoing trials examining the benefit of cetuximab in the management of NSCLC Track 10 Potential role of combining biologic agents in NSCLC Track 11 Efficacy and tolerability of bevacizumab in ECOG-E4599 Track 12 Potential role of bevacizumab in the adjuvant setting Track 13 Incorporation of biologic agents into the management of Stage III disease Track 14 Maintenance chemotherapy for patients with Stage III disease Track 15 Clinical experience with bevacizumab Track 16 Impact of smoking status on approach to treatment Track 17 Continuation of bevacizumab after disease progression Track 18 Impact of cost on the selection of cancer therapies Track 19 Accrual to clinical trials in lung cancer

Select Excerpts from the Interview

Track 2

DR KIM: ECOG-E4599 was a two-arm randomized trial of carboplatin/paclitaxel with or without bevacizumab. Patients received up to six cycles of chemotherapy. Patients on the bevacizumab arm received it concurrently with chemotherapy and then as maintenance after completing six cycles (Sandler 2005).

ECOG-E4599 included more than 800 patients, and the results indicated a survival benefit of greater than two months (3.1). It’s the first trial in NSCLC to add an agent to an existing chemotherapy regimen and show a survival advantage. Median survival was more than 12 months, which is the first time that’s been demonstrated (Sandler 2005).

The study we are conducting at MD Anderson evaluates carboplatin/docetaxel and bevacizumab as first-line therapy for patients with NSCLC (3.2). This trial will supplement the data from ECOG-E4599 to show feasibility of bevacizumab with other platinum-based doublets.

Track 3

DR KIM: Currently, to my knowledge, docetaxel and paclitaxel are the only taxanes evaluated in combination with bevacizumab in lung cancer. Data for gemcitabine/cisplatin in combination with bevacizumab may be available by the end of the year. We’re not sure yet if any carboplatin with gemcitabine data will become available, although I’m sure that trial is planned. I’m unsure whether any of the nab paclitaxel studies are ready to evaluate bevacizumab.

Track 7

DR KIM: At MD Anderson, in cooperation with Dana-Farber and Emory, we are planning to perform a series of Phase II trials. We will mandate that patients receiving second-line therapy undergo two core biopsies. After completing the biopsies, we are asking them to wait for two weeks. At that point, we will conduct a litany of biomarker tests, including VEGF-related, EGF-related, including mutation and amplification, and others, like cyclin D1, RAS and RAF kinase.

We will put these data into a statistical model that’s being developed by one of our top statisticians, Dr Jack Lee at MD Anderson, and derive a hypothetical score. If the patient’s tumor, based on preclinical data, favors a VEGF type of inhibition, that patient will then be randomly assigned to a VEGF trial we have open.

The four drugs we will be evaluating are erlotinib, ZD6474 (Zactima), erlotinib plus bexarotene — because we’ve seen synergistic activities described at Dartmouth (Dragnev 2004) — and then sorafenib, as the final arm. So, based on the characteristics of a patient’s tissue, we will hypothetically try to place them in a drug arm that is most favorable to their tumor. The best-case scenario is that we get much higher response rates and disease control than has been described in other Phase II studies. The worst-case scenario is that we’ve randomly placed a patient into a trial with one of four very active drugs for non-small cell lung cancer. So it’s a “win-win” from that standpoint.

DR LOVE: How much extra morbidity or risk will there be in getting more tissue?

DR KIM: There’s always a risk any time you perform a procedure on a patient. In breast cancer they have made major strides because they were able to obtain tissue and do validated arrays. The problem we have in lung cancer is that we have no validation of arrays, because, frankly, we don’t have much tissue to test in these metastatic patients.

We tell patients that they will have an opportunity to receive one of these four promising drugs and be followed closely. In fact, if they progress on one of these arms, we retest their tissue, if they allow us, and see if they may fit into a different arm.

DR LOVE: What if the patient asks, “How much extra risk am I going to take, and what are the risks of those procedures?”

DR KIM: The major risk is doing a core biopsy. That may be a bronchoscopy or a CT-guided core biopsy. The risks — particularly at our center for doing these in lesions that are reasonably sized, greater than one centimeter, somewhat peripheral — as far as pneumothorax or lung collapse — are very low, in the realm of one percent.

Track 12

DR KIM: Bevacizumab works well in the metastatic setting, so there is a rationale to move our best metastatic regimen to adjuvant therapy. If you go with the published data, cisplatin/vinorelbine is the regimen that you would choose to add bevacizumab to in the adjuvant setting. However, not many people are using cisplatin/vinorelbine as adjuvant therapy. I personally prefer cisplatin/docetaxel.

With bevacizumab, you need to consider the problems that could occur in a postoperative setting. We have to derive that from the colon trials. We’re not sure if there will be any wound dehiscence in lung cancer patients who have had surgery.

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