Phase III study of BEC2/BCG vaccination in limited disease small cell lung cancer (LD-SCLC) patients, following response to chemotherapy and thoracic irradiation (EORTC 08971, the SILVA study)

Abstract

7020 Background: Attempts to maintain the response to initial therapy have been unsuccessful in SCLC. BEC2 is a murine IgG2b antibody that elicits antiidiotypic response to GD3, a glycosphingolipid overexpressed on membranes of SCLC and other tumors derived from the neural crest. In a pilot study (Grant et al. Clin Cancer Res 1999) long-term survivors were reported in SCLC patients vaccinated with BEC2/BCG. Methods: LD-SCLC patients in response after 4–6 cycles of multi-agent chemotherapy and thoracic irradiation were eligible. PCI was recommended in complete responders. Patients were randomized to observation or to 5 BEC2 (Merck KGaA and ImClone Systems Inc.) vaccinations (2.5 mg by 8 intradermal injections) with BCG, given on week 0, 2, 4, 6 and 10. A total of 376 deaths were required to detect a 40% increase in median survival in the V arm using a 2-sided α of 5% and a 90% power. The protocol was amended after 55% of inclusions to allow patients with a PPD positive test, when this was found to be safe (Klimek et al, ASCO 2000).Results: From April 1998 to October 2002 515 patients were randomized to observation (O, n=258) or vaccination (V, n=257). Arms were well balanced; 38% female, Karnofsky PS >80% in 94%, PPD positive in 11%, complete response to initial therapy in 49%, sequential chemotherapy-thoracic irradiation in 40%; 62% received PCI. The most frequent treatment related side effect was local reaction at the injection sites (95% of patients, grade 3 in 35%). Lethargy was observed in 37% (grade 3 in 3%). Six toxic deaths have been reported, 4 in the O arm (1 radiation pneumonitis and 3 pancytopenia) and 2 in the V arm (2 radiation pneumonitis). So far 71% of patients have progressed and 72% have died. There was no difference in survival (median 16.3 vs 14.3 months, p=0.3) or progression-free survival (median 6.6 vs 5.7 months, p=0.2) between O and V arms. Conclusions: Vaccination with BEC2/BCG does not provide any survival advantage in limited disease SCLC patients after a major response to induction chemo-radiation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck & Co., Inc.