In the phase 3, randomized, open-label CASPIAN study, first-line Durvalumab ( Imfinzi ) added to Etoposide plus either Cisplatin or Carboplatin ( EP ) significantly has improved overall survival ( OS ) versus EP alone ( hazard ratio, HR 0.73 [ 95% CI 0.59–0.91 ]; p = 0.0047 ) in patients with extensive-stage small cell lung cancer ( ES-SCLC ) at the planned interim analysis.
Researchers have described treatment patterns and outcomes for patients according to brain metastases.
Treatment-naïve patients ( WHO PS 0/1 ) with ES-SCLC received 4 cycles of Durvalumab 1500 mg + EP q3w followed by maintenance Durvalumab 1500 mg q4w until disease progression ( PD ) or up to 6 cycles of EP q3w and optional prophylactic cranial irradiation ( PCI; investigator’s discretion ).
Patients with either asymptomatic or treated and stable brain metastases were eligible.
Brain imaging was suggested for patients with suspected brain metastases, but was not mandated at screening or during treatment.
The primary endpoint was overall survival. Analysis of overall survival and progression-free survival ( PFS ) in patient subgroups with and without brain metastases was prespecified.
Other analyses in these subgroups were post hoc.
Data cutoff: Mar 11, 2019.
At baseline, 28 ( 10.4% ) of 268 patients in the Durvalumab + EP arm and 27 ( 10.0% ) of 269 patients in the EP arm had known brain metastases; of these, only 3 patients ( ~11% of those with baseline brain metastases ) in each arm received radiotherapy ( RT ) to the brain prior to study entry.
Durvalumab + EP consistently improved overall survival versus EP in patients with or without known brain metastases at baseline ( HR 0.69 [ 95% CI 0.35–1.31 ] and 0.74 [ 0.59–0.93 ], respectively ); progression-free survival was also consistently improved with Durvalumab + EP regardless of the presence or not of baseline brain metastases ( HR 0.73 [ 0.42–1.29 ] and 0.78 [ 0.64–0.95 ] ).
Among patients without known brain metastases at baseline, similar proportions developed new brain metastases at first progression disease in the Durvalumab + EP ( 20/240; 8.3% ) and EP arms ( 23/242; 9.5% ), despite 19 ( 7.9% ) patients in the EP arm having received prophylactic cranial irradiation.
Overall, 48 of 268 ( 17.9% ) and 49 of 269 ( 18.2% ) patients in the Durvalumab + EP and EP arms received RT to the brain subsequent to study treatment; rates remained similar across the Durvalumab + EP and EP arms regardless of baseline brain metastases ( 11 of 28 [ 39.3% ] and 11 of 27 [ 40.7% ] patients with known baseline brain metastases, compared to 37 of 240 [ 15.4% ] and 38 of 242 [ 15.7% ] patients without known baseline brain metastases ).
In conclusion, in CASPIAN, overall survival and progression-free suvival outcomes were improved with Durvalumab + EP versus EP regardless of baseline brain metastases, consistent with the ITT analyses.
Rates of new brain metastases at first progression disease were similar between arms, although prophylactic cranial irradiation was permitted only in the control arm.
Rates of subsequent radiotherapy to the brain were also similar in both arms. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020