In the PEARLS/KEYNOTE-091 trial, adjuvant pembrolizumab substantially improved DFS vs placebo in the subgroup of patients with stage IB, II, or IIIA NSCLC who received adjuvant platinum-based chemotherapy following complete resection.¹ The IMpower010 trial showed a DFS benefit with atezolizumab vs best supportive care after adjuvant chemotherapy in patients with resected stage II–IIIA NSCLC, with pronounced benefit in the subgroup of patients whose tumour PD-L1 expression was 1% or more.²

Abbreviations

DFS, disease-free survival; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1.

References

1. Oselin K, et al. J Clin Oncol 2023;41;8520.
2. Felip E, et al. Lancet. 2021;398:1344–57

The current NCCN guidelines recommend atezolizumab as an adjuvant therapy option for eligible patients with PD-L1 levels of 1% or more who are also negative for certain biomarkers (EGFR exon 19 deletions, EGFR exon 21 L858R mutations, and ALK rearrangements) and who have previously received adjuvant chemotherapy based on clinical trial data and FDA approval. 

Abbreviations

NCCN, National Comprehensive Cancer Network; PD-L1, programmed death-ligand 1.

Reference

NCCN. Clinical Practice Guidelines in Oncology 2024. Non-small cell lung cancer. Version 6.2024. Available at: www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 20 June 2024).

The NCCN guidelines recommend that all patients should be evaluated for neoadjuvant immunotherapy with strong consideration for those with node-positive disease or tumour diameter of 4 cm or more and no contraindications for immune checkpoint inhibitors. However, neoadjuvant therapy should not be used to attempt to induce resectability in patients who do not already meet criteria for resectability on initial evaluation.

Abbreviation

NCCN, National Comprehensive Cancer Network.

Reference

NCCN. Clinical Practice Guidelines in Oncology 2024. Non-small cell lung cancer. Version 6.2024. Available at: www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 20 June 2024).

The NCCN guidelines recommend atezolizumab as an adjuvant therapy option for eligible patients with completely resected stage IIB to IIIA, stage IIIB (only T3, N2), or high-risk stage IIA NSCLC and with PD-L1 expression of 1% or more, who are negative for EGFR aberrations and ALK rearrangements, and who have previously received adjuvant chemotherapy.  

Abbreviations

NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1.

Reference

NCCN. Clinical Practice Guidelines in Oncology 2024. Non-small cell lung cancer. Version 6.2024. Available at: www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 20 June 2024).

The phase III AEGEAN trial assessed perioperative durvalumab + neoadjuvant chemotherapy, vs neoadjuvant chemotherapy alone. Patients with known EGFR/ALK aberrations were excluded from the efficacy analyses in the modified intent-to-treat population.¹ An exploratory analysis of patients with EGFR-mutated resectable NSCLC showed minimal benefit of neoadjuvant durvalumab in this population: the unstratified EFS HR was 0.86 (95% CI, 0.35–2.19; vs modified intent-to-treat population: stratified HR, 0.68; 95% CI, 0.53–0.88; p=0.003902). PCR and MPR of the EGFR-mutated subgroup were 3.8% and 7.7%  vs 17.2% and 33.3% in the modified intent-to-treat population.¹ The CheckMate 77T trial also excluded patients with EGFR mutations or known ALK translocations.² Molecular testing was not mandated in the KEYNOTE-671 trial, and very few patients with EGFR mutations or ALK translocations were identified, a situation that limited any insights in these subgroups.³

NCCN guidelines recommend testing for PD-L1 status, EGFR mutations and ALK rearrangements for patients with stages IB–IIIA, IIIB [T3,N2], and exclusion of EGFR mutations and ALK rearrangements is recommended prior to consideration for neoadjuvant nivolumab plus chemotherapy.⁴ 

Abbreviations

CI, confidence interval; EFS, event-free survival; HR, hazard ratio; MPR, major pathological response; NSCLC, non-small cell lung cancer; PCR, pathological complete response.

References

1. He J, et al. J Thorac Oncol. 2023;18(Suppl. 11):S72–3.
2. Cascone T, et al. N Engl J Med. 2024;390:1756–69.
3. Wakelee H, et al. N Engl J Med. 2023;389:491–503.
4. NCCN. Clinical Practice Guidelines in Oncology 2024. Non-small cell lung cancer. Version 6.2024. Available at: www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 20 June 2024).