Trevor M. Feinstein, MD, Examines Docetaxel With or Without Plinabulin in Stage IIIB/IV EGFR Wild-Type NSCLC

The phase 3 DUBLIN-3 trial (NCT02504489) aimed to determine if use of docetaxel with plinabulin could improve efficacy and safety outcomes vs docetaxel alone for patients with EGFR wild-type stage IIIB/IV non–small cell lung cancer.^1,2

Trevor M. Feinstein, MD, a medical oncologist in hematology and internal medicine at the Piedmont Cancer Institute in Atlanta, Georgia, and lead investigator of this study spoke, with CancerNetwork^® about research from the study presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Two posters were made available, one related to patient subgroup analyses and the other focusing on patients’ quality of life as measured using European Organisation for the Research and Treatment of Cancer Core Quality of Life Core 30 (QLQ-C30) questionnaire and the modular lung cancer supplement QLQ-LC13.

Overall, it was determined that quality of life was improved when plinabulin was added to docetaxel.

CancerNetwork^®: What was the rationale for the DUBLIN-3 research?

Feinstein: DUBLIN-3 was a large phase 3 trial done in advanced non–small cell lung cancer. Prior to this, there was an earlier phase 1 trial that expanded to phase 1b looking at the role of plinabulin combined with docetaxel. In that small trial, they saw that in patients who had measurable disease in the lung had increased progression-free survival [when treated with the combination].³ That led into DUBLIN-3 and exploring that further.

Research from a subgroup analysis in nonsquamous NSCLC was presented at ASCO. Can you lend some context to this?

That was abstract 9090, and that looked at nonsquamous [NSCLC]. When we looked at it, we saw that in the squamous population, there were 5 patients who had hemoptysis. We know that plinabulin might have some VEGF activity, so we wanted to look at the nonsquamous population. There we saw an improvement in survival from a point of 8.8 months to 11.4 months, which was thought-provoking there.

What was found when quality of life was investigated in DUBLIN-3?

There were 2 ways we looked at quality life. At ESMO [the European Society for Medical Oncology Congress], we presented with QTWiST, which is quality-adjusted time without symptoms [of disease of toxicity] before progression.⁴ We saw with the addition of plinabulin to docetaxel, the quality-of-life QTWiST has increased by over 18%. Now, at this year’s ASCO, we looked at patient-reported outcomes of quality life and the 2 different measures there. In the first 10 cycles, we didn’t find any difference in the quality of life. Between cycles 10 and 20, you start to see the curve separating and by cycle 20 they became significant. Now, we saw that patients who received plinabulin had less coughing, dysphasia, and sore throat. You did see that with the additional plinabulin and there was increased hemoptysis. What I also found interesting is that patients who received plinabulin received more cycles of docetaxel and there was no reported increase in neuropathy despite getting more cycles of docetaxel. Otherwise, the quality of life we saw earlier at ESMO [resulted in] decreased neutropenia with addition of plinabulin.

Are there any future analyses planned based on results from DUBLIN-3?

From this research, what we’d look at would be a subgroup analysis. There was a large Chinese patient population to look at to see if that’s any difference [vs other patient populations]. At ESMO, we tried to present a Western patient population to show some of that information pulled from some other studies. I don’t know if we’re going to go any further and look at this as a mutational analysis.

What do you hope your colleagues took away from these presentations?

What I’d hoped people would take away is that the future is interesting in lung cancer, and we’ve seen some dramatic changes. Docetaxel is still considered standard care, unfortunately, after platinum [therapy] and after immunotherapy. It’s nice to see that there can be some combinations mixed with docetaxel that might reduce some of the toxicity making a better-tolerated treatment in the second or third line.

References

1. Feinstein T, Ogenstad S, Mitchell D, et al. DUBLIN-3 results on quality of life (QoL) in second/third-line EGFR-wild type NSCLC patients (pts) receiving docetaxel (Doc) with or without plinabulin (Plin) using the validated EORTC QLQ C30 and QLQ LC13 questionnaires. J Clin Oncol. 2022;40(suppl 16):9091. doi:10.1200/JCO.2022.40.16_suppl.9091
2. Han B, Feinstein T, Shi Y, et al. Subgroup analysis in patients (pts) with non-squamous (N-Sq), EGFR-wild type (wt), second/third-line NSCLC from the global phase (Ph) 3 trial DUBLIN-3 (BPI-2358-103) with the plinabulin/docetaxel (Plin/Doc) combination versus Doc alone. . J Clin Oncol. 2022;40(suppl 16):9090. doi:10.1200/JCO.2022.40.16_suppl.9090
3. Millward M, Mainwaring P, Mita A, et al. Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel. Invest New Drugs. 2012;30(3):1065-1073. doi:10.1007/s10637-011-9642-4
4. Feinstein T, Han B, Shi Y, et al. DUBLIN-3 (BPI-2358-103): A global phase (Ph) III trial with the plinabulin/docetaxel (Plin/Doc) combination vs. Doc in 2nd/3rd Line NSCLC patients (pts) with EGFR-wild type (wt) progressing on a prior platinum-based regimen. Annal Oncol. 2021;32(suppl 5):S1283-S1246. doi:10.1016/annonc/annonc741