Pembrolizumab ups survival in NSCLC patients with liver or brain metastases
Pembrolizumab in combination with pemetrexed and platinum chemotherapy significantly improves overall survival (OS) and progression-free survival (PFS) vs chemotherapy alone in patients with untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) with liver or brain metastases, a post hoc analysis of the phase III KEYNOTE-189 trial has shown.
“Interestingly, similar OS and PFS benefits were observed with pembrolizumab in patients with liver or brain metastases compared with the overall population,” said investigator Dr Marina Garassino of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, who presented the results at the American Association for Cancer Research (AACR) Annual Meeting 2019 in Atlanta, Georgia, US. “This suggests that liver or brain metastasis should not be used as an exclusion criterion in selecting patients [for pembrolizumab therapy].” [Garassino MC, et al, AACR 2019, abstract CT043]
In KEYNOTE-189, 616 patients with untreated metastatic nonsquamous NSCLC without EGFR or ALK alterations were randomized to receive pemetrexed and platinum chemotherapy in combination with pembrolizumab (n=410) or placebo (n=206). Randomization was stratified by PD-L1 expression (tumour proportion score <1 percent vs ≥1 percent), platinum chemotherapy (cisplatin vs carboplatin), and smoking history (never vs former/current smoker).
At baseline, 66 patients (16 percent) had liver metastases, while 73 patients (18 percent) had brain metastases. Twenty-five patients had both liver and brain metastases. The trial’s primary endpoints were OS and PFS.
Results of the post hoc analysis, reported after a median follow-up of 18.7 months, showed a significant improvement in OS among those treated with pembrolizumab plus chemotherapy vs chemotherapy alone (median, 12.6 months vs 6.6 months; hazard ratio [HR], 0.62; 95 percent confidence interval [CI], 0.39 to 0.98). PFS was likewise improved with pembrolizumab plus chemotherapy (median, 6.1 months vs 3.4 months with chemotherapy alone; HR, 0.52; 95 percent CI, 0.34 to 0.81).
The OS and PFS benefits with pembrolizumab were similar in patients without liver metastases at baseline, with HRs of 0.58 (95 percent CI, 0.45 to 0.74) and 0.48 (95 percent CI, 0.39 to 0.59), respectively.
Among patients with brain metastases, median OS was 19.2 months in those treated with pembrolizumab plus chemotherapy vs 7.5 months in those treated with chemotherapy alone (HR, 0.41; 95 percent CI, 0.24 to 0.67).
“A median OS of 19.2 months is very long for patients with brain metastases,” remarked Garassino. “In these patients, median PFS was 6.9 months with pembrolizumab plus chemotherapy vs 4.7 months with chemotherapy alone [HR, 0.42; 95 percent CI, 0.27 to 0.67].”
In patients with no brain metastases at baseline, HRs for OS and PFS were 0.59 (95 percent CI, 0.46 to 0.75) and 0.48 (95 percent CI, 0.39 to 0.59), respectively, also favouring pembrolizumab.
These results are consistent with those of the primary analysis, which showed similar improvements in OS (HR, 0.49; 95 percent CI, 0.38 to 0.64) and PFS (HR, 0.52; 95 percent CI, 0.43 to 0.64) in the pembrolizumab vs placebo group (both p<0.001), as well as a manageable safety profile with pembrolizumab plus chemotherapy. [N Engl J Med 2018;378:2078-2092]
“The pembrolizumab/chemotherapy combination was generally tolerable among patients with or without liver or brain metastases at baseline,” reported Garassino. “The post hoc analysis revealed no new safety signals, with no unexpected immune-related adverse events or infusion reactions.”
“Liver and brain metastases are common in NSCLC and associated with poor prognosis. These new results establish pembrolizumab as standard of care for patients with untreated metastatic nonsquamous NSCLC, irrespective of baseline status of liver or brain metastasis,” Garassino concluded.