Adding pembrolizumab to perioperative chemotherapy improves EFS in early-stage NSCLC

Neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab improved event-free survival (EFS) in patients with early-stage non-small cell lung cancer (NSCLC) compared with neoadjuvant chemotherapy and surgery alone, as shown by the results from KEYNOTE-671.

PD-1 and PD-L1 inhibitors are standard-of-care treatment for advanced and metastatic NSCLC. Although recent phase 3 trials have shown benefit of PD-(L)1 inhibitors given before or after resection in early-stage NSCLC, many patients still experience recurrence [1–3]. A perioperative approach including both neoadjuvant and adjuvant PD-(L)1 inhibition may provide a benefit beyond either approach alone.

The phase 3 KEYNOTE-671 trial (NCT03425643) evaluated the efficacy and safety of perioperative pembrolizumab in patients with resectable stage II, IIIA, or IIIB NSCLC. Prof. Heather Wakelee (Stanford University, CA, USA) presented the first results [4].

The study randomised 797 participants 1:1 to neoadjuvant pembrolizumab plus chemotherapy (i.e. cisplatin/gemcitabine or cisplatin/pemetrexed) followed by surgery and adjuvant pembrolizumab (pembrolizumab arm) or to neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo arm).

EFS was significantly increased in the pembrolizumab arm compared with the placebo arm (HR 0.58; P<0.00001). EFS rate at 24 months was 62.4% versus 40.6%, respectively. The benefit of pembrolizumab was observed in all prespecified subgroups. Participants with PD-L1 expression ≥1% had more benefit compared with patients with PD-L1 expression <1% (HR 0.51 vs HR 0.77). Overall survival data are not yet mature but showed a trend favouring pembrolizumab (HR 0.73; P=0.021).

Both complete and major pathological response was increased in the pembrolizumab arm compared with placebo (18.1% vs 4.0% and 30.2% vs 11.0%, respectively). Exploratory analysis showed an EFS benefit for perioperative pembrolizumab regardless of whether patients achieved complete or major pathologic response.

“Data from KEYNOTE-671 supports neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab as a potential new treatment option for patients with resectable stage II, IIIA, or IIIB NSCLC,” concluded Prof. Wakelee.

1. Forde PM, et al. N Engl J Med 2022;386:1973–1985.
2. Felip E, et al. Lancet 2021;398:1333–1357.
3. O’Brien M, et al. Lancet Oncol. 2022;23:1274–1286.
4. Wakelee HA, et al. KEYNOTE-671: randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early-stage NSCLC. Abstract LBA100, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 2 August, 202315 February, 2024