Unmet Needs in the Treatment of Lung Cancer - Episode 4

Subgroup Analyses for Nab-Paclitaxel in NSCLC

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The phase III CA031 trial demonstrated dramatic improvements in overall survival (OS) for elderly patients with advanced non-small cell lung cancer (NSCLC) treated with first-line nab-paclitaxel plus carboplatin, when compared with solvent-based (sb) paclitaxel plus carboplatin. In the study, the median OS in patients over age 70 was 19.9 months with nab-paclitaxel compared with 10.4 months with sb-paclitaxel. However, progression-free survival and overall response rate (ORR) were not statistically significantly extended in this population, raising concerns regarding the authenticity of this benefit, notes D. Ross Camidge, MD, PhD.

In the study, sb-paclitaxel was administered once every 3 weeks while nab-paclitaxel was administered weekly. The 3-week dosing schedule for sb-paclitaxel could have indirectly impacted efficacy through added toxicity, since studies have demonstrated that weekly paclitaxel has a favorable nonhematologic toxicity profile with similar efficacy. A study looking at carboplatin in combination with either weekly nab-paclitaxel or weekly paclitaxel in elderly patients could help further define the benefits seen in the CA031 trial, panelists believe.

In the broader frontline population, nab-paclitaxel offers an option for patients. Moreover, the medication is easier to administer than sb-paclitaxel, since it does not require premedication, Ramaswamy Govindan, MD, states. These differences could stem from evidence suggesting that nab-paclitaxel may not be a taxane, like paclitaxel. More research is needed to further explore the mechanism of action, Govindan believes.

In CA031, ORR was substantially extended with nab-paclitaxel for patients with squamous histology, at 41% versus 24%. However, in non-squamous histology, ORR was similar (26% vs 25%). These findings suggest nab-paclitaxel has the most utility in patients with squamous histology.

Outside of the squamous subset, nab-paclitaxel is also useful for patients who can't tolerate steroids or are hypersensitive to paclitaxel, notes Alice T. Shaw, MD, PhD. The potential ability to avoid the need for the coadministration of steroids with nab-paclitaxel makes it a preferential therapy for combination studies with checkpoint inhibitors, adds Camidge.

Future studies are looking at nab-paclitaxel as a maintenance therapy in patients with squamous NSCLC. The abound trial is exploring 4 cycles of weekly nab-paclitaxel and carboplatin followed by maintenance nab-paclitaxel or best supportive care. The weekly schedule in this study could help mitigate some of the toxicity commonly seen with every-3-weeks sb paclitaxel, notes Corey J. Langer, MD.