Nivolumab is FDA approved and recommended by the NCCN for the treatment of adults with resectable (tumours ≥4 cm or node positive) NSCLC in the neoadjuvant setting, in combination with platinum-doublet chemotherapy.^1,2 In May 2023, the EMA CHMP adopted a positive opinion recommending a change in the marketing authorization for nivolumab,³ which has been subsequently approved by the EMA for the neoadjuvant treatment of adults with resectable NSCLC at high risk of recurrence and a PD-L1 expression of  ≥1%.⁴

Abbreviations

CHMP, Committee for Medicinal Products for Human Use; EMA, European Medicines Agency; FDA, US Food & Drug Administration; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer, PD-L1, programmed death-ligand 1.

References

1. FDA. Nivolumab Prescribing Information. 2023. Available at: https://bit.ly/3HAqZOb (accessed 25 April 2023).
2. NCCN. Non-small cell lung cancer. V3.2023. Available at: https://bit.ly/3N8WDVc (accessed 7 June 2023).
3. EMA. 2023. CHMP post-authorisation summary of positive opinion for nivolumab (II-117). Available at: https://bit.ly/3PP1aPp (accessed 7 July 2023).
4. EMA. Nivolumab SmPC. Available at: https://bit.ly/437B9ht (accessed 30 June 2023).

The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable stage III NSCLC and no disease progression after concurrent chemoradiotherapy.¹ At median follow-up of 61.6 months for censored patients (median follow-up for all patients was 34.2 months), median OS and PFS were greater with durvalumab than placebo (mOS: 47.5 vs 29.1 months; mPFS: 16.9 vs 5.6 months).¹ OS and PFS benefit favoured durvalumab vs placebo across all PD-L1 subgroups, with the exception of OS in patients with a PD-L1 expression of <1%.¹

Both the NCCN and ESMO guidelines recommend up to 12 months of consolidation immunotherapy with durvalumab for patients with unresectable stage II/III NSCLC, performance score 0–1, PD-L1 expression ≥1% (ESMO only²) and no disease progression after definitive concurrent chemoradiation.^2,3

Abbreviations

ESMO, European Society for Medical Oncology; m, median; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival.

References

1. Spigel DR, et al. J Clin Oncol. 2022;40:1301–11.
2. Remon J, et al. Ann Oncol. 2021;32:1637–42.
3. NCCN. Non-small cell lung cancer. V3.2023. Available at: https://bit.ly/3N8WDVc (accessed 7 June 2023).

Although PD-L1 expression is currently used to guide treatment decisions and regulatory approval, several key limitations remain.¹

• PD-L1 expression shows both spatial (inter- and intra-tumour) and temporal heterogeneity, resulting in discordant PD-L1 status between samples and over the clinical course.¹
• Not all patients with high PD-L1 expression respond to anti-PD-1/PD-L1 therapy; responses have been seen in patients with low or negative PD-L1 scores.^2–4
• PD-L1 expression is a continuous rather than binary (positive vs negative) variable; arbitrary cut-offs are required to use PD-L1 as a biomarker, which may undermine its predictive power depending on the stringency of the cut-off.⁵

Abbreviations

NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1.

References

1. Wang M, et al. J Thorac Dis. 2020;12:4541–8.
2. Rittmeyer A, et al. Lancet. 2017;389:255–65.
3. Antonia SJ, et al. N Engl J Med. 2017;377:1919–29.
4. Carbone DP, et al. N Engl J Med. 2017;376:2415–26.
5. Meyers DE, et al. Curr Oncol. 2018;25:e324–34.

Pembrolizumab monotherapy is approved by both the FDA and EMA and recommended by the NCCN and ESMO for the first-line treatment of metastatic NSCLC in patients with a PD-L1 expression of ≥1%¹ or ≥50%^2–4 and no EGFR or ALK positive tumour mutations.^1,2,4 Neither nivolumab monotherapy nor durvalumab monotherapy are FDA or EMA approved in this setting.^1,2

Abbreviations

ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ESMO, European Society for Medical Oncology; FDA, US Food and Drug Administration; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1.

References

1. FDA. PI for all agents available at: https://bit.ly/42WdeBv (all accessed 15 June 2023).
2. EMA. SmPC for all agents listed available at: https://bit.ly/3CPrWPT (all accessed 15 June 2023).
3. NCCN. Non-small cell lung cancer. V3.2023. Available at: https://bit.ly/3N8WDVc (accessed 7 June 2023).
4. Hendriks LE, et al. Ann Oncol. 2023;34:358–76.

A 4-year clinical update of the CheckMate-9LA trial, which tested first-line nivolumab plus ipilimumab with chemotherapy vs chemotherapy alone in patients with metastatic NSCLC were presented at the 2023 ASCO Annual Meeting. Data showed that nivolumab plus ipilimumab with chemotherapy continued to provide long-term, durable OS benefit compared with chemotherapy alone in all randomized patients. Durable efficacy benefit of combination immunotherapy was observed regardless of tumour PD-L1 expression or histology (squamous or non-squamous).

Abbreviations

ASCO, American Society of Clinical Oncology; NSCLC, non-small cell lung cancer; OS, overall survival; PD-L1, programmed death-ligand 1.

Reference

Carbone DP, et al. J Clin Oncol. 2023;41:LBA9023.