Efficacy of Platinum Pemetrexed in EGFR+ NSCLC Post-Osimertinib

September, 09, 2024 | Lung Cancer, NSCLC (Non-Small Cell Lung Cancer)

KEY TAKEAWAYS

  • The OCELOT phase 2 trial aimed to investigate the efficacy of 2L platinum pemetrexed chemotherapy in patients with EGFR+ aNSCLC.
  • The primary endpoint was to determine ORR and the secondary outcome was PFS and TTF.
  • Researchers noticed that platinum pemetrexed offers comparable efficacy in patients with EGFR+ aNSCLC.

Platinum doublet chemotherapy remains a standard treatment for patients with epidermal growth factor receptor mutation-positive (EGFR+) advanced non-small cell lung cancer (aNSCLC) who experience disease progression on osimertinib. However, there is a lack of evidence from pragmatic clinical trials evaluating second-line (2L) platinum chemotherapy following osimertinib.

Saurav Verma and the team aimed to assess the efficacy of 2L platinum pemetrexed chemotherapy in patients with EGFR+ aNSCLC who progressed after osimertinib.

They performed an inclusive analysis of the OCELOT (NCT04335292) clinical trial, a multicentered phase II open-label study. This trial evaluated osimertinib as a third-line (3L) treatment for EGFR+ aNSCLC in 2 cohorts: Cohort A, which included patients receiving osimertinib as first-line (1L) treatment followed by platinum-pemetrexed chemotherapy as 2L treatment, and Cohort B, which involved patients with uncommon EGFR mutations receiving osimertinib as 1L treatment.

Patients in Cohort A were enrolled during their 2L chemotherapy phase, while those in Cohort B were enrolled prior to initiating 1L osimertinib. The study analyzed response rates according to RECIST 1.1 criteria, along with survival outcomes for patients treated with platinum-pemetrexed chemotherapy after progression on osimertinib. Chemotherapy dosing was determined at the investigator’s discretion. The primary outcome was the objective response rate (ORR), while secondary outcomes included progression-free survival (PFS) and time to treatment failure (TTF).

About 29 patients received 2L treatment with platinum pemetrexed at the data cut-off for this analysis. Of these, 52% (n = 15) were male, with a median age of 63 years (range, 36-87 years). Among the patients, 22 had evaluable disease. The ORR for the entire cohort was 31.8%, and the disease control rate (DCR) was 81.8%, with 7 patients achieving a partial response, 11 experiencing stable disease, and 4 showing progressive disease.

For the 6 patients with uncommon EGFR mutations, the ORR was 50% (n = 3), and the DCR was 83% (n = 5). The median PFS for the whole cohort was 6.6 months, with a 6-month PFS rate of 50% (this result remained consistent when restricted to common mutations). The median TTF was 7.0 months, and the 6-month TTF was 53.3%. Overall survival (OS) data remain immature.

The study concluded that the response rate and PFS for patients with EGFR+ aNSCLC treated with 2L platinum pemetrexed after progression on osimertinib are comparable to those reported in the published literature. This finding supports that the benefits of platinum pemetrexed are applicable to a pragmatic patient population receiving chemotherapy dosed at the investigators’ discretion.

The trial was sponsored by Mark Vincent.

Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/1284

Clinical Trial: https://clinicaltrials.gov/study/NCT04335292

Verma S, Vincent M.D, Liu G, et al. (2024). “Efficacy of Platinum Pemetrexed in Patients with EGFR Mutated Advanced Lung Cancer after Progression on Osimertinib – A Prospective Cohort Study.” Presented at: World Conference on Lung Cancer (WCLC); September 8, 2024; Singapore.

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