Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy, subsequently concomitant with radiotherapy (RT) in patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC). Analysis of survival and value of ctDNA for patient selection
Por:
Provencio M, Majem M, Guirado M, Massuti B, de las Penas R, Ortega A, Domine M, Marse R, Sala M, Paredes A, Moran T, Vazquez S, Coves J, Larriba J, Sanchez J, Vicente D, Farre N, Fornos L, Zapata I, Franco F, Serna-Blasco R, Romero A, Isla D
Publicada:
1 mar 2021
Resumen:
Background: Little progress has been achieved in non-small cell lung cancer (NSCLC) patients with unresectable stage III disease and new drug schemes are warranted.
Material and methods: In this open-label, single-arm, phase II trial 65 treatment-naive stage III NSCLC deemed surgically unresectable by a multidisciplinary team were treated with 2 cycles of induction cisplatin at 80 mg/m(2) every 21 days plus metronomic oral vinorelbine at 50 mg/day every Monday, Wednesday and Friday. During the concomitant treatment with thoracic radiotherapy cisplatin was administered in the same manner but oral vinorelbine was reduced to 30 mg/day. The objective was to administer a total radiotherapy dose of 66 Gy in 33 daily fractions of 2 Gy. The primary endpoint was progression-free survival (PFS). Correlation between circulating tumor DNA (ctDNA) levels and survival was also evaluated.
Results: Fifty-five (78.5 %) patients completed treatment. Overall response rate, by RECIST criteria, was 66.2 %. Four (6.2 %) patients had complete response, 39 (60.0 %) partial response and 12 (18.5 %) stable disease. Seven patients (10.8 %) had progressive disease during the induction period. Median follow-up was 29.1 months (m), median PFS was 11.5 m (95 %CI: 9.6-15.4). PFS at 12 m in the intention-to-treat (ITT) population was 47.8 % (95 %CI: 35.1-59.4 %) and median OS was 35.6 m (95 %CI: 24.4-46.8). Grade >= 3 treatment-related adverse events occurred in 14 (21.5 %) patients during induction and in 13 (24.5 %) patients during concomitant treatment with esophagitis occurring in 3% and pneumonitis in 1.5 % of the patients. Patients with undetectable ctDNA after 3 m follow-up had median PFS and OS of 18.1 m (95 %CI: 8.8-NR) and not reached (NR) (95 %CI: 11.3-NR), respectively, compared with 8.0 m (95 %CI: 2.7-NR) and 24.7 m (95 %CI: 5.7-NR) for patients who remained ctDNA positive at that time point.
Conclusions: Metronomic oral vinorelbine and cisplatin obtains similar efficacy results with significantly lower toxicity than the same chemotherapy at standard doses. ctDNA can identify populations with particularly good prognosis.
Filiaciones:
Provencio M:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol, Majadahonda, Spain
Majem M:
Hosp Univ Santa Creu & St Pau, Med Oncol, Barcelona, Spain
Guirado M:
Hosp Gen Univ Elche, Med Oncol, Elche, Spain
Massuti B:
Hosp Gen Univ Alicante, Med Oncol, Alicante, Spain
de las Penas R:
Consorcio Hosp Prov Castellon, Med Oncol, Castellon de La Plana, Spain
Ortega A:
Hosp Univ Jaen, Med Oncol, Jaen, Spain
Domine M:
Hosp Univ Fdn Jimenez Diaz, IIS FJD, Med Oncol, Madrid, Spain
Marse R:
Hosp Univ Son Espases, Med Oncol, Palma De Mallorca, Spain
Sala M:
OSI Bilbao Basurto, Med Oncol, Bilbao, Spain
Paredes A:
Hosp Univ Donostia, Med Oncol, San Sebastian, Spain
Moran T:
Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Catalan Inst Oncol Badalona,Dept Med, Med Oncol,Inst Germans Trias & Pujol,Badalona App, Badalona, Spain
Vazquez S:
Hosp Univ Lucus Augusti, Med Oncol, Lugo, Spain
Coves J:
Hosp Univ Son Llatzer, Med Oncol, Palma De Mallorca, Spain
Larriba J:
Hosp Univ Clin San Carlos, Med Oncol, Madrid, Spain
Sanchez J:
Hosp La Princesa, Med Oncol, Madrid, Spain
Vicente D:
Hosp Univ Virgen de la Macarena, Med Oncol, Seville, Spain
Farre N:
Hosp Univ Santa Creu & St Pau, Radiat Oncol, Barcelona, Spain
Fornos L:
Hosp Gen Univ Alicante, Radiotherap Oncol, Alicante, Spain
Zapata I:
Hosp Univ Puerta Hierro, Radiat Oncol, Majadahonda, Spain
Franco F:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol, Majadahonda, Spain
Serna-Blasco R:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol, Majadahonda, Spain
Biomed Sci Res Inst Puerta Hierro Majadahonda, Liquid Biopsy Lab, Majadahonda, Spain
Romero A:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol, Majadahonda, Spain
Biomed Sci Res Inst Puerta Hierro Majadahonda, Liquid Biopsy Lab, Majadahonda, Spain
Isla D:
IIS Aragon, Hosp Clin Univ Lozano Blesa, Med Oncol, Zaragoza, Spain
|