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Clinical Trial
. 2021 Feb;124(4):721-727.
doi: 10.1038/s41416-020-01141-8. Epub 2020 Nov 25.

Adding cetuximab to paclitaxel and carboplatin for first-line treatment of carcinoma of unknown primary (CUP): results of the Phase 2 AIO trial PACET-CUP

Gunnar Folprecht  1 , Karolin Trautmann  2 , Alexander Stein  3 , Gerdt Huebner  4 , Michael Stahl  5 , Stefan Kasper  6 , Albrecht Kretzschmar  7 , Claus-Henning Köhne  8 , Viktor Grünwald  9   10 , Ralf-Dieter Hofheinz  11 , Katharina Schütte  2 , Harald Löffler  12 , Carsten Bokemeyer  3 , Alwin Krämer  13 ; Arbeitsgemeinschaft Internistische Onkologie (AIO) - CUP Group
Affiliations
Clinical Trial

Adding cetuximab to paclitaxel and carboplatin for first-line treatment of carcinoma of unknown primary (CUP): results of the Phase 2 AIO trial PACET-CUP

Gunnar Folprecht et al. Br J Cancer. 2021 Feb.

Abstract

Background: Patients with carcinoma of unknown primary (CUP) have a dismal prognosis, even when treated with multi-agent chemotherapy. We hypothesised that adding the epidermal growth-factor receptor (EGFR) inhibitor cetuximab to standard first-line chemotherapy with paclitaxel and carboplatin would improve PFS and RR in unfavourable CUP.

Methods: This open-labelled, multicentre Phase 2 study included patients with unfavourable, untreated adeno- or undifferentiated CUP. Patients were randomised to receive either paclitaxel/carboplatin (group A) or paclitaxel/carboplatin plus cetuximab (group B) every 3 weeks for a maximum of 6 cycles followed by cetuximab maintenance in group B. The primary endpoint was PFS in the two groups. Secondary endpoints were RR, toxicity and overall survival (OS).

Results: One-hundred-and-fifty patients were randomised (group A = 72, group B = 78). The median PFS and OS for all patients were 3.8 and 8.1 months (95% confidence interval (CI): 2.9-4.8 and 6.8-9.5). There was no significant difference in PFS (3.7 vs 4.6 months, HR 0.98) or OS (8.1 vs 7.4, HR 1.1) between the two treatment groups. Response rate tended to be better for chemotherapy plus cetuximab compared to chemotherapy alone (22% vs 15%). Adverse events grade ≥3 were comparable between the two groups, except for significantly increased skin toxicity in the cetuximab arm.

Conclusions: Cetuximab plus paclitaxel/carboplatin did not improve PFS, OS and RR in metastatic CUP compared to paclitaxel/carboplatin alone. Addition of cetuximab resulted in additional skin toxicity.

Clinical trial registration: The study was registered at clinicaltrials.gov as NCT00894569.

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Conflict of interest statement

G.F. received a study grant by Merck and honoraria for lectures and advisory board meetings from Merck, Roche, Amgen, Lilly, Sanofi-Aventis, Servier, Bayer, BMS and MSD. K.T. received honoraria for lectures and advisory board meetings from BMS, Celgene, Takeda, GSK, Servier and Janssen-Cilag. A.S. received research grants from Merck, BMS, Roche, Sanofi, Servier, German Cancer Aid and Federal Joint Committee, and honoraria for lectures and advisory board meetings by Merck, Roche, Amgen, Lilly, Sanofi-Aventis, Servier, Bayer, BMS, MSD and Sirtex. G.H. received honoraria for lectures and advisory board meetings by BMS, Sanofi-Aventis, Novartis, Roche and Boehringer Ingelheim. M.S. received honoraria for lectures from Merck and Amgen. SK received financial support for conduction of clinical trials by Merck, BMS; Roche, Celgene and Lilly and received honoraria for lectures and advisory board meetings from Merck, Roche, Amgen, Lilly, Sanofi-Aventis, Servier, Bayer, BMS, MSD and GSK. A.K.R.E. received honoraria for lectures and advisory board meetings or travel support for medical conference attendance by Merck, Roche, Amgen, Sanofi-Aventis, Servier, BMS and MSD. C.H.K. received a study grant and honoraria for lectures and advisory board meetings from Merck, Roche, Amgen, Lilly, Sanofi-Aventis, Servier, Bayer, BMS, MSD and Novartis. V.G. acted as an advisor for BMS, MSD, Merck Serono, AstraZeneca, Novartis, Pfizer, Ipsen, Cerulean, EUSA-Pharm., Roche and Nanobiotix and received compensation for lectures from BMS, MSD, Merck Serono, AstraZeneca, Novartis, Pfizer, Ipsen, Eisai, Roche, PharmaMar, Lilly, Janssen-Cliag and Exelexis. He received research grants from AstraZeneca, BMS, MSD, Pfizer and Ipsen. C.B. received honoraria for lectures and advisory board meetings from Lilly, Merck, Sanofi, Roche Mundipharma, Bayer, Hexal, GSO, BMS, Servier, Pfizer and AstraZeneca. A.K.R.Ä. received research support by Bayer and Merck Serono, study grants by Merck and BMS and honoraria for lectures and advisory board meetings, as well as reimbursement for study-related travels by Roche and Daiichi-Sankyo. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Progression-free and overall survival according to treatment arm.
The graphs show the progression-free survival and overall survival probability for patients in arms A (blue dotted line) and B (red solid lines).
Fig. 2
Fig. 2. Treatment efficacy according to subgroups.
The Forrest plots describe the Oddʼs ratio for patients with complete or partial remission (a) and the Hazard ratio for progression free survival (b) or overall survival (c) according to the baseline parameters (univariat analysis). * interaction between baseline parameter and treatment arm.
See this image and copyright information in PMC

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