Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Phase III trial results suggest that the PD-1 inhibitor sintilimab may improve progression-free survival (PFS) compared with placebo when given to patients undergoing first-line chemotherapy for locally advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC).
The ORIENT-11 results were presented at the 2020 Virtual Presidential Symposium of the World Congress on Lung Cancer by Li Zhang, from Sun Yat-sen University Cancer Center in Guangzhou, China.
Median PFS was 8.9 months for the 266 patients who were randomly allocated to receive four cycles of sintilimab 200 mg alongside pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC5 every 3 weeks, followed by the same doses of sintilimab and pemetrexed in 3-week cycles for up to 24 months.
This was significantly longer than the median PFS of 5.0 months for the 131 patients who instead received placebo with the chemotherapy regimen, giving a significant hazard ratio (HR) of 0.48 in favour of the sintilimab combination. Patients were allowed to cross over to sintilimab on progression.
Forest plot analysis confirmed the PFS benefit in most subgroups, although this did not reach significance for female patients and those with brain metastases.
Analysis by PD-L1 tumour proportion score showed a significant median PFS benefit with sintilimab versus placebo for patients with a score of 1–49% (7.1 vs 4.8 months, HR=0.50) or 50% and above (not reached vs 5.0 months, HR=0.31), but not those with a score of less than 1% (7.3 vs 5.1 months, HR=0.66).
Median overall survival (OS) has not been reached in either arm but interim analysis indicates a possible benefit, reported Li Zhang, with 6-month OS achieved by 89.6% of sintilimab-treated patients versus 80.4% of controls, giving a significant HR of 0.61.
Compared with placebo, sintilimab also achieved a better overall response rate (51.9 vs 29.8%) and disease control rate (86.8 vs 75.6%) and a longer median duration of response (unreached vs 5.5 months).
Li Zhang described the sintilimab regimen as having a “manageable safety profile” with “no new safety signals”.
The majority of patients in both the sintilimab and placebo groups completed four cycles of chemotherapy (88.3 vs 83.2%), with median treatment durations of 7.0 and 5.9 months, respectively.
Patients given sintilimab plus chemotherapy had similar rates to those given placebo plus chemotherapy of grade 3–5 adverse events (AEs, 61.7 vs 58.8%), serious AEs (28.2 vs 29.8%) and grade 3–5 immune-related AEs (5.6 vs 6.1%).
The most common adverse events were anaemia, neutropenia and leukopenia associated with chemotherapy, Li Zhang said.
Session discussant Misako Nagasaka, from Wayne State University in Detroit, Michigan, USA, noted that the ORIENT-11 trial included only patients from East Asia, and thus gives data on the immunotherapy–chemotherapy combination in a population that was underrepresented in the KEYNOTE-189 trial.
While acknowledging that ORIENT-11 OS data are yet to mature, she suggested the median PFS values appear comparable to those of KEYNOTE-189 and those of other immunotherapy studies in this setting.
Nevertheless, Misako Nagasaka emphasized the need for longer follow-up to confirm that the sintilimab PFS benefit will translate into an OS gain.
Reference
Zhang L, Yang Y, Wang Z, et al. ORIENT-11: Sintilimab + pemetrexed + platinum as first-line therapy for locally advanced or metastatic non-squamous NSCLC. WCLC Virtual Presidential Symposium 2020; 8 August 2020.
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