Episode 3: Adjuvant Pembrolizumab for Early-Stage NSCLC After Resection and Optional Chemotherapy: the PEARLS trial
Presented by Prof Mariana Brandao (Institut Jules Bordet) and Prof Johan Vansteenkiste (University Hospitals Leuven)
Professor Mariana Brandao, a medical oncologist at Institut Jules Bordet in Brussels, and Professor Johan Vansteenkiste from University Hospitals Leuven are pleased to announce a new episode of WND in lung cancer.
Immunotherapy has established itself as the standard for stage IV and resectable stage III cases and significant progress occurs in the surgical and adjuvant settings. Recently, updated findings from the PEARLS trial were presented at the ESMO IO meeting in Geneva. In this randomised phase 3 trial, pembrolizumab is investigated versus placebo as adjuvant therapy for completely resected stage IB-IIIA NSCLC.
The median follow-up period at the time of analysis was 51.7 months. The initial analysis of this trial, which included 1200 patients, was published in The Lancet in 2022 and showed a significant enhancement in DFS, the primary endpoint, with a median DFS of 53.6 months for pembrolizumab compared to 42 months for the placebo group, representing an HR of 0.76.
Unexpectedly, patients with high PD-L1 expression did not perform well in terms of HR in the trial, likely due to the superior performance of the standard arm.
The updated analysis demonstrated a significant difference in the ITT population: the 4-year OS rate was 52% for pembrolizumab and 45% for the placebo arm. Additionally, a meaningful difference was observed in all subgroups. With all subgroups showing a benefit in favour of pembrolizumab, the EMA recently approved its use in post-surgical resection and adjuvant chemotherapy in patients with resected NSCLC, regardless of PD-L1 expression. Moreover, the treatment is now reimbursed in Belgium.
Both experts concur on the significant opportunity this creates for offering immunotherapy to patients post-surgery and chemotherapy. It is crucial to note that chemotherapy was not obligatory in the PEARLS trial. However, almost 15-20% of patients who did not receive chemotherapy had a hazard ratio of 1.15, indicating a less favourable outcome. This underscores the importance for clinicians to consider adjuvant chemotherapy whenever feasible for stage II and IIIA resected NSCLC.
It is essential to communicate this to patients, some of whom may prefer to receive immunotherapy directly, despite the complexities of chemotherapy side effects.
The outcome of this trial in the adjuvant setting prompts discussion about how to approach pembrolizumab for stage II patients, especially considering recent data demonstrating benefits in the peri-operative setting. The primary concern is that approximately 50% of patients who undergo neoadjuvant treatment do not proceed to surgery. Thus, in a straightforward scenario for surgery in stage II patients, opting for the adjuvant approach would be advisable, even though preclinical data may favour the neoadjuvant approach. This decision is complex and requires thorough discussion with the patient.
References:
Besse B et al. (2023) Adjuvant Pembrolizumab versus Placebo for Early-Stage NSCLC After Resection and Optional Chemotherapy: Updated Results From PEARLS/KEYNOTE-091. ESMO IO2023 #120MO