You are here: Home: LCU 2 | 2007: Craig Reynolds, MD

Tracks 1-11

Track 1 Introduction Track 2 Development of novel TKIs in NSCLC Track 3 Combination therapy with bevacizumab and erlotinib Track 4 Predictors of response to the EGFR TKIs Track 5 Phase II trial of carboplatin, nab paclitaxel and bevacizumab for patients with nonsquamous-cell NSCLC Track 6 Secreted protein acidic and rich in cysteine (SPARC), caveolin-1 and enhanced delivery of nab paclitaxel Track 7 Clinical trial results with MUC1 and MAGE vaccines in NSCLC Track 8 Clinical research strategies to identify targets for chemotherapy and novel agents Track 9 Evaluation of the novel anthracycline amrubicin in the treatment of SCLC Track 10 Incorporation of bevacizumab into the treatment of NSCLC Track 11 Lung cancer in smokers and nonsmokers: Implications for treatment approaches

Select Excerpts from the Interview

Track 4

DR REYNOLDS: I believe there are a couple ways you can look at it. One is to view it from a clinical physician standpoint and say female patients are more likely to respond than male patients, Asians are more likely to respond than non-Asians and nonsmokers are much more likely to respond than smokers. In general, using these clinical factors can provide a good estimate of the likelihood of response. That does not mean that a male smoker with squamous cell carcinoma has no chance of benefit from erlotinib, but the likelihood of a huge benefit is much less.

Another view is from the biology perspective, and a few ideas have been investigated. One is EGFR gene amplification. That work has been conducted predominantly by Fred Hirsch at Colorado, and his team has shown fairly compellingly that overexpression of the EGFR gene in tumors predicts response and survival in lung cancer.

The other part of the biology equation has been EGFR mutations, with research pioneered primarily by Tom Lynch at Harvard. He has been able to show certain mutations, particularly an exon 19 deletion, for example, that tend to predict good response to therapy (Jackman 2006; [4.1]).

Every clinician who has used erlotinib or gefitinib extensively has most likely had one or two patients who have done incredibly well on the drug. I feel that gene amplification is a better predictor of the group of patients that derives meaningful benefit from the drug but not the spectacular home run we occasionally see.

Tracks 5-6

DR REYNOLDS: We conducted a single-arm Phase II trial evaluating the combination of bevacizumab, nab paclitaxel and carboplatin in nonsquamous NSCLC, and this trial was developed after the results of ECOG-E4599 became available (Sandler 2006). In fact, we were developing the trial without bevacizumab and then thought the combination of nab paclitaxel and bevacizumab offered promise for lung cancer patients.

Rakesh Jain compellingly suggested with his research (Willett 2004) that one of the major roles of bevacizumab in improving outcomes has to do with improving drug delivery into tumors by changing tumor oncotic pressure and normalizing vasculature. Compelling preclinical and early clinical data with nab paclitaxel show that the formulation of nab paclitaxel does a better job of tumor drug delivery, so we thought the combination of these two drugs would potentially improve outcomes.

We embarked on a single-arm Phase II trial with entry criteria that were fairly similar to those used in ECOG-E4599, and the results we have seen are promising. Thus far with 50 patients, response rates are in the range of 30 percent, and we did not see any toxicity different from what we would expect based on ECOG-E4599.

DR LOVE: How much of an advantage is the shorter infusion time with nab paclitaxel (4.2)?

DR REYNOLDS: The shortened time in the office is significant, especially when you are dealing with patients who will only live about another year.

DR LOVE: What is the next step in terms of studying nab paclitaxel?

DR REYNOLDS: The current strategy is to embark on a Phase III trial. Whether that trial will involve bevacizumab is still a matter of debate, although I believe the study that will go forward is standard paclitaxel with carboplatin versus nab paclitaxel with carboplatin for advanced lung cancer treatment. The possibility of a study in the adjuvant setting has also been discussed.

We have to be careful to ask questions that benefit our patients, and my enthusiasm for using these engineered taxanes in general has to do with the possibility of improving outcomes. Compelling data with at least a couple of these drugs indicate better delivery into the tumor and therefore potentially improved outcomes.

Select Publications

Table of Contents

Top of Page