The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to results presented at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer held in Barcelona, Spain, the presence of secondary ALK mutations did not appear to influence the overall response rate (ORR) for patients receiving the ALK inhibitor, alectinib, in the phase 3 ALUR study (ClinicalTrials.gov Identifier: NCT02604342) which compared alectinib with chemotherapy in patients with ALK-positive advanced non-small cell lung cancer (NSCLC) previously treated with 2 lines of therapy, including crizotinib and platinum-based chemotherapy.1

Specifically, the ALUR study was an open-label, randomized trial in which 119 patients with ALK-positive, crizotinib-resistant, advanced/recurrent NSCLC were randomly assigned in a 2:1 ratio to receive alectinib, an ALK inhibitor, versus docetaxel or pemetrexed monotherapy. The primary end point of the study was progression-free survival (PFS).

Related Articles

A primary analysis of ALUR study results published in 2018 demonstrated significantly improved PFS and a more favorable safety profile for patients receiving alectinib compared with chemotherapy.2   

In this study, the researchers performed a final analysis of the study data regarding efficacy and safety. In addition, targeted genomic sequencing was performed retrospectively using either tumor tissue (33 individuals) or baseline plasma specimens (59 individuals) to evaluate the ALK status (ie, the presence of ALK fusions or secondary ALK mutations) of the disease.

Similar to the previously-reported results from the primary analysis of the ALUR trial, median PFS was 10.9 months and 1.4 months in the alectinib and chemotherapy arms, respectively (hazard ratio [HR], 0.20; 95% CI, 0.12-0.33; P <.001). Furthermore the ORR was 66.7% for patients receiving alectinib versus 0% for those treated with chemotherapy (P <.001). Notably, the ORR in the CNS was 50.6% and 2.5% in the alectinib and chemotherapy arms, respectively (P <.001).

Although no significant difference in overall survival (OS) was observed between study arms, the crossover rate for patients in the chemotherapy arms was nearly 90%.

Differences in the safety profiles between the 2 study arms included a treatment discontinuation rate in the chemotherapy arm that was more than twice that observed in the alectinib arm (10.8% vs 5.2%). Furthermore, the rates of grade 3 or higher treatment-related adverse events were 37.7% with alectinib and 43.2% with chemotherapy, although the duration of treatment with alectinib was longer.

The presence of ALK fusions were confirmed retrospectively in 78.8% and 69.5% of available tissue and plasma specimens, respectively. For those patients with disease demonstrated to be positive for an ALK fusion, the ORR was 72.2% and 63.0% for those with tumor tissue samples and plasma specimens, respectively.

Although secondary ALK mutations were detected in 27.1% plasma specimens, the ORR was similar for alectinib-treated patients with ALK fusion-positive disease with or without these alterations (60.0% versus 64.7%).  However, alterations in other genes were associated with a lower ORR.

In their concluding remarks, the study authors stated that “the role of reconfirming ALK status upon sequential ALK inhibitor treatment requires further investigation, due to the limited data and known technical challenges of plasma testing.”

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

References

  1. Wolf J, Helland A, Oh I-J, et al. Phase 3 ALUR study of alectinib in pretreated ALK+ NSCLC; Final efficacy, safety and targeted genomic sequencing analyses. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA02.07.
  2. Novello S, Mazières J, Oh IJ, et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018;29(6):1409-1416.