POSEIDON Immunotherapy Plus Chemotherapy Approach Improves Metastatic NSCLC Survival

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The use of the PD-L1 inhibitor durvalumab, with or without the CTLA-4 inhibitor tremelimumab, alongside an investigator’s choice of platinum-based chemotherapy may offer a novel strategy for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC), research suggests. 

Melissa Johnson, from the Sarah Cannon Research Institute in Nashville, Tennessee, USA, reported the findings on behalf of the POSEIDON investigators at the World Congress on Lung Cancer 2021 virtual meeting. 

The presenter highlighted that the trial participants were mainly recruited from Eastern Europe and Asia and that there was a higher proportion of squamous NSCLC patients than usually seen in a mixed histology group, making up 36.2–37.9% of the treatment groups. 

The primary endpoint of progression-free survival (PFS) was significantly higher in the 338 patients who were randomly assigned to receive durvalumab plus chemotherapy than the 337 patients given chemotherapy alone, at a median 5.5 versus 4.8 months and a hazard ratio (HR) of 0.74. 

There was also a trend towards improved overall survival (OS) with use of durvalumab, at a median 13.3 versus 11.7 months with chemotherapy alone, although the HR of 0.86 did not reach statistical significance, the presenter said. 

The secondary endpoint of PFS in the 338 patients given durvalumab plus tremelimumab and chemotherapy versus those given chemotherapy alone significantly favoured the combination arm, with a median duration of 6.2 versus 4.8 months and a HR of 0.72. 

And this benefit was mirrored in the OS analysis, with corresponding median durations of 14.0 and 11.7 months and a significant HR of 0.77 in favour of durvalumab plus tremelimumab and chemotherapy. 

Melissa Johnson emphasized that the addition of tremelimumab led to “improved separation of the curves with the characteristic flattening of the curve that we have to come to look for with the addition of anti-CTLA-4 agents.” 

She continued that, when compared with durvalumab and chemotherapy, the inclusion of tremelimumab further improved landmark 12-month PFS (26.6 vs 24.4%) and 24-month OS (32.9 vs 29.6%) rates from that achieved by chemotherapy only (PFS=13.1%, OS=22.1%). 

Most patient subgroups derived an OS gain from the addition of immunotherapy to chemotherapy, the presenter reported, with patients with nonsquamous histology or a tumour PD-L1 expression level of less than 1% especially benefiting from the additional use of tremelimumab. 

Moreover, use of durvalumab alone or with tremelimumab plus chemotherapy significantly improved the objective response rate compared with chemotherapy alone (odds ratio=2.26 and 2.00, respectively) and extended the median duration of response (7.0 and 9.5 vs 5.1 months).  

At 12 months, 38.9% of patients given durvalumab and 49.7% of patients given durvalumab plus tremelimumab had an ongoing response compared with 21.4% of controls. 

The majority (95.5%) of nonsquamous histology patients in the study received pemetrexed plus platinum chemotherapy and they derived a significant PFS benefit with use of immunotherapy versus chemotherapy alone, with the greatest improvement achieved with tremelimumab. 

Median OS was significantly greater with use of durvalumab plus tremelimumab alongside chemotherapy (17.2 vs 13.1 months, HR=0.70) while there was a nonsignificant improvement with durvalumab only (14.8 months, HR=0.82). 

Of the squamous histology patients, 88.3% received gemcitabine plus platinum chemotherapy but PFS and OS were “poor across all treatment arms with little separation of the curves”, observed Melissa Johnson. 

Discussing the safety data, the presenter said the majority of patients in all three treatment arms received at least four cycles of treatment and went on to receive maintenance pemetrexed. She noted that the median number of durvalumab doses was eight in both immunotherapy arms and 66.1% of patients given tremelimumab received five doses. 

“There were no new safety signals”, the investigator said and “most events were driven by the chemotherapy.” 

There was a slightly higher rate of treatment-related grade 3–4 adverse events in the durvalumab plus tremelimumab arm than in the durvalumab only and control arms (51.8 vs 44.6 and 44.4%, respectively) but the rates of discontinuation and death were comparable across the groups. 

Summarising the findings, the presenter concluded: “Durvalumab plus tremelimumab plus chemotherapy represents a potential new front-line treatment option for metastatic NSCLC.” 

Reference 

Johnson ML, Cho BC, Luft A, et al. Durvalumab ± tremelimumab + chemotherapy as first-line treatment for mNSCLC: Results from the phase 3 POSEIDON study. 2021 World Conference on Lung Cancer; 8–14 September.