Pembrolizumab–Etoposide Offers Long-Term ‘Clinically Meaningful Improvement’ In ES-SCLC Survival

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The latest survival results from the KEYNOTE-604 trial have been reported to the IASLC World Conference on Lung Cancer 2022 and confirm the efficacy of pembrolizumab plus etoposide as a first-line regimen for patients with extensive-stage small-cell lung cancer (ES-SCLC). 

After a median 43.3 months of follow-up, the combination “continued to show clinically meaningful improvement in OS [overall survival] and PFS [progression-free survival]” compared with placebo plus etoposide, reported Charles Rudin, from Memorial Sloan Kettering Cancer Center in New York, USA, at the meeting held in Vienna, Austria. 

The study compared four 3-week cycles of pembrolizumab 200 mg (n=228) or placebo (n=225) on day 1 given alongside etoposide 100 mg/m2 on days 1–3 plus carboplatin or cisplatin, with pembrolizumab or placebo continued for up to 31 further cycles. All patients were eligible for prophylactic cranial irradiation when indicated. 

OS analysis in the intention-to-treat population gave a hazard ratio (HR) for death of 0.76 in favour of immunotherapy, with 15.5% of pembrolizumab-treated patients alive at 36 months versus 5.9% of controls. The median OS in the arms was 10.8 and 9.7 months, respectively. 

Similar, the HR for disease progression or death was 0.70 in favour of pembrolizumab, with 36-month PFS rates of 6.9% in the pembrolizumab arm versus 0.5% in the placebo arm. Median duration of PFS was 4.8 and 4.3 months, respectively. 

Charles Rudin highlighted that while the median duration of response was similar in the pembrolizumab and control arms (4.2 versus 3.7 months), 11.5% of patients given pembrolizumab continued to respond at 36 months and 10.1% at 42 months, compared with 0.9% of controls at both timepoints. 

The presenter noted that 18 patients successfully completed all 35 cycles of pembrolizumab and these individuals did not appear to differ from other participants with regard to age, sex, target lesion size and other baseline factors. 

These participants achieved a complete (n=2) or partial (n=16) response to treatment and the median duration of response was unreached, with all patients continuing to respond after 12 months and 83.3% after 24 months.  

Median OS in this patient subgroup was unreached and 72.2% were alive 2 years after completing pembrolizumab therapy, reported Charles Rudin, adding that 77.8% of patients were alive as of last assessment, as were both (0.9%) of the patients who completed 35 cycles of placebo. 

The presenter said the KEYNOTE-604 results “support the continued exploration of pembrolizumab-based combinations for the treatment of ES-SCLC”, such as in the ongoing KEYVIBE-008 study comparing first-line treatment with pembrolizumab–vibostolimab versus atezolizumab, both given in combination with chemotherapy. 

Session discussant Virginie Westeel, from Hôpital Jean Minjoz in Besançon, France, said the long-term results of the KEYNOTE-604 trial “confirm the current standard treatment” for ES-SCLC of platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. 

But she observed that the findings also “outline the need for biomarkers to better select patients who will benefit from [immunotherapy]”. 

Reference 

OA12.06: Kim HR, Navarro A, Gottfried M, et al. First-line pembrolizumab or placebo combined with etoposide and platinum for ES-SCLC: KEYNOTE-604 long-term follow-up. IASLC World Conference on Lung Cancer 2022; Vienna, Austria: 6–9 August.