NACT is increasingly used as a model to explore new targeted therapy in combination with CT in AOC. Whether an intermediate endpoint could be used as surrogate of PFS and/or OS in pts treated with ...NACT remains currently elusive and was explored retrospectively in the CHIVA trial.
Patients (pts) with FIGO stage IIIC-IV AOC considered as unresectable after laparoscopic (Lap) evaluation were treated with 3 to 4 cycles of platinum-taxane NACT + oral nintedanib before interval debulking surgery (IDS). CT (up to 6 cycles in total) and nintedanib were pursued post-operatively. Were measured response rates at the end of NACT according to RECIST (ORR) with CT-scan and to GCIG with CA125, initial Peritoneal Cancer Index (PCI) and its evolution at IDS, complete surgical resection rate (CC0), pathologic complete or near complete response rate (pCR). These covariates in univariate analysis were included together with other prognostic clinical covariates:age, FIGO stage, ECOG, tumor size, ascitis, neutrophil/lymphocyte ratio, platelet and hemoglobin counts and symptoms (pain).
A total of 163/188 pts included in the CHIVA trial were evaluable for the analysis. Median follow-up is 42. 6 mos (95% CI: 39.9-44.8). In the univariate Cox model, ECOG, ascitis, neutrophil/lymphocyte ratio, PCI at baseline, RECIST ORR, CC0 at IDS, pCR and treatment arm were correlated (p<0.05) to PFS and/or OS. In the multivariate Cox model, RECIST ORR (p<0.01) and CC0 at IDS (p<0.01) were the only variables predictive of both PFS and OS. The median PFS was respectively 10.4, 15.1 and 18.3 mos among the 3 groups of pts with 1) No ORR and no CC0; 2)only CC0 or only ORR; 3)ORR and CC0. PFS Hazard Ratio was 0.33 0.20; 0.52, 0.43 0.32; 0.70 and 0.68 0.44; 1.06 for group 3v1, 2vs1 and 2v3 respectively. Median OS was 25.4, 41.0 mos and not reached for group 1, 2, and 3 respectively (p<0.001).
Results from the CHIVA trial suggest that the rate of patients who achieve both a RECIST response to NACT and a complete surgical resection (CC0) at IDS could be used as the main primary endpoint for future NACT trials.
2011-006288-23.
ARCAGY-GINECO.
Boehringer Ingelheim.
F. Lecuru: Advisory / Consultancy, Board: AstraZeneca; Advisory / Consultancy, Proctoring: Intuitive Surgical. E. Pujade-Lauraine: Honoraria (self), Self: AstraZeneca; Honoraria (self), Self: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Tesaro. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. N. Dohollou: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly. A. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. C. Louvet: Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.
Long term information on the risk/benefit ratio of currently available therapies remains crucial for treatment decisions. In the PACS04 phase III trial, patients (pts) with node-positive (N+) breast ...cancer (BC) were double-randomized to concomitant taxane-anthracycline versus standard FEC, as well as 1-year trastuzumab versus nill in the HER2+ subpopulation.
3009 pts (20% HER2+, 12% triple negative (TNBC) BC) were randomly assigned to receive 6 cycles of fluorouracil 500mg/m2, epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 (FEC) or epirubicin 75mg/m2 and docetaxel 75mg/m2 (ED). Pts with HER2+ tumors were randomized to either trastuzumab (TRA) for one year, or observation (OBS). The primary endpoint was disease-free survival (DFS).
After a median 115-month follow-up, DFS was not different in the ED compared to the FEC arm (70% vs 68% respectively, HR=0.88 95% CI: 0.77-1.01; p=0.064), nor was OS: 80% with FEC and 81% with ED (HR=0.97 95% CI: 0.81-1.16; p=0.729). Subgroup analysis suggested better DFS with ED in non-TNBC pts HR=0.82 (0.71-9.96) p=0.02. In the 528 pts with HER2+ BC, there was trend for a higher DFS in the TRA arm (68%; 95% CI: 61-74) versus the OBS arm (60%; 95% CI: 54-66); HR=0.77 95% CI:0.57-1.03; p=0.079 (intent to treat population). In the per protocol population, DFS, but not OS, was significantly higher in the TRA arm (HR: 0.69 95%CI: 0.51-0.94; p=0.0156). ED led to more neurological and hematological toxicities (31% vs 11% febrile neutropenia) and led to 5 versus 1 treatment-related deaths. During follow-up, 75 pts developed a second non-breast primary cancer (43 with FEC and 32 with ED); 12 were hematologic malignancies (7 with FEC and 5 with ED). Long term cardiac deaths were rare (3 with FEC and 1 with ED).
This study did not show superiority of the concomitant anthracycline-taxane arm, which was more toxic in high-risk N+ BC pts. Long-term results of the HER2+ subpopulation are in line with the other adjuvant TRA trials but less striking probably due to lack of power. Long term cardiac toxicity and second primary cancer rate are similar to what has been reported by others.
NCT00054587.
UNICANCER. 101 rue Tolbiac, 75013 Paris, France.
Roche, Ligue Nationale Contre le Cancer.
All authors have declared no conflicts of interest.
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