Pembrolizumab shows meaningful improvement in DFS as adjuvant therapy for stage IB-IIIA NSCLC

In the PEARLS/KEYNOTE-091 study, a randomized, triple-blinded phase 3 trial, pembrolizumab demonstrated an improved disease-free survival (DFS) as adjuvant therapy in patients with completely resected stage IB-IIIA non-small cell lung cancer (NSCLC) vs. placebo.1 

The current standard treatment for stage IB-IIIA NSCLC is surgery, followed by adjuvant chemotherapy.2 Yet, emerging studies have highlighted the role of other adjuvant therapies such as immunotherapies in improving DFS in these patients.3,4 Pembrolizumab, a programmed death-1 receptor blocker (anti-PD-1), has previously been shown to be effective in improving survival and clinical outcomes as a first-line treatment for NSCLC with a significant programmed death-ligand 1 (PD-L1) expression.5 The PEARLS/KEYNOTE-091 trial further investigated the role of pembrolizumab in the adjuvant setting of stage IB-IIIA NSCLC with any PD-L1 expression levels.1

The trial recruited 1,177 patients aged ≥18 years from 196 medical centers across 29 countries, with any pathologically confirmed NSCLC of stage IB-IIIA as per the American Joint Committee on Cancer (AJCC) staging system that has been completely surgically resected and has a known PD-L1 expression status.1 Adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease as per the local guidelines.2 Participants were randomized into the pembrolizumab group or the saline placebo group, given intravenously every 3 weeks until recurrence, having other clinically adverse events (AEs), or completion of 18 administrations.1 The primary endpoints included DFS in the overall population and the subpopulation with a PD-L1 tumor proportion score (TPS) of ≥50%.1 In both populations, the median ages were 65 years, with most patients having previously received 3 or 4 cycles of adjuvant chemotherapy with a cisplatin and/or carboplatin-based regimen.1 The median follow-up was 35.6 months.1

In the overall population, 212 of 590 patients (36%) and 260 of 587 patients (44%) in the pembrolizumab and placebo groups, respectively, had a DFS event, with the median DFS being 53.6 months in the pembrolizumab group and 42.0 months in the placebo group (HR=0.76; 95% CI=0.63-0.91; p=0.0014).1 Within the population of PD-L1 TPS ≥50%, 54 of 168 patients (32%) and 63 of 165 patients (38%) in the pembrolizumab and placebo groups, respectively, had a DFS event (HR=0.82; 95% CI: 0.57-1.18).1 In both populations, the most common DFS event was recurrence.1

The rates of treatment-related serious adverse events (TEAEs) in the pembrolizumab and placebo groups were 12% (n=68) and 2% (n=13), respectively, with pneumonitis (2%; n=12) and diarrhea (1%; n=6) being the most common among patients treated with pembrolizumab, and pneumonitis (1%; n=3), and colitis (<1%; n=2) in the placebo arm.1

To conclude, adjuvant pembrolizumab monotherapy showed significant and clinically meaningful improvement in DFS vs. placebo in stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of PD-L1 expression.1 Yet, a longer follow-up is warranted to determine whether the DFS benefit with pembrolizumab will translate into an overall survival (OS) benefit.1

  1. O’Brien M, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB–IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286.
  2. Postmus PE, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl 4):iv1-21.
  3. Wu YL, et al. Osimertinib in resected EGFR-mutated non–small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723.
  4. Felip E, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-1357.
  5. Aguilar EJ, et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol. 2019;30(10):1653-1659.

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