21 februari 2018

Panitumumab aanvullend op gemcitabine en cisplatin faalt bij galwegenkanker met KRAS wild type (dus geen KRAS mutatie). Uit een studie emt totaal 90 patiënten bleek de medinae overall voerleivng maar liefst 8 maanden minder in de groep van de panitumumab in vergelijking emt de groep die geen panitumumab kregen als chemotherapie. Hier faalt een check pointremmer - anti-PD medicijn dus.

Ik ga het niet vertalen maar dit waren de belangrijkste conclusies (abstract staat onderaan:

This phase II study was designed to evaluate the combination of panitumumab plus gemcitabine/cisplatin in patients with advanced KRAS wild-type biliary cancer. Patients were randomized two to one to receive gemcitabine/cisplatin with or without panitumumab. The progression-free survival rate at 6 months (the primary endpoint) was 54% in the cisplatin/gemcitabine/panitumumab arm and 73% in the cisplatin/gemcitabine without panitumumab arm. The objective response rate (a secondary endpoint) was 45% in the cisplatin/gemcitabine/panitumumab arm compared with 39% in the non-panitumumab arm; overall survival (the other secondary endpoint) was 12.8 months and 20.1 months in the two arms, respectively.
The addition of panitumumab did not result in an improved objective response rate or longer progression-free or overall survival.

Klik op de titel voor het studierapport:

PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer—a randomised biomarker-driven clinical phase II AIO study

Hier het abstract van de studie:

The addition of panitumumab did not result in an improved objective response rate or longer progression-free or overall survival.

PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer—a randomised biomarker-driven clinical phase II AIO study

Arndt Vogel

Correspondence information about the author Arndt Vogel

Email the author Arndt Vogel

Stefan Kasper

Michael Bitzer

Andreas Block

Marianne Sinn

Henning Schulze-Bergkamen

Markus Moehler

Nicole Pfarr

Volker Endris

Benjamin Goeppert

Kirsten Merx

Elisabeth Schnoy

Jens T. Siveke

Patrick Michl

Dirk Waldschmidt

Jan Kuhlmann

Michael Geissler

Christoph Kahl

Ralph Evenkamp

Torben Schmidt

Alexander Kuhlmann

Wilko Weichert

Stefan Kubicka

DOI: https://doi.org/10.1016/j.ejca.2017.12.028

Highlights

•Panitumumab was evaluated in KRAS wild-type patients with biliary cancer.
•Addition of EGFR antibody to standard chemotherapy does not improve outcome of patients.
•Molecular profiling identified p53 and IDH1/2 mutation as most common genetic alteration in our patient population.
•IDH1/2 mutations might predict benefit from platin-based chemotherapy, which should be explored in prospective trials.

Abstract

Background

Combination chemotherapy has shown benefit in the treatment of biliary cancer and further improvements might be achieved by the addition of a biological agent. We report here the effect of chemotherapy with the monoclonal EGFR antibody panitumumab as therapy for KRAS wild-type biliary cancer.

Patients and methods

Patients with advanced biliary tract cancer were randomised (2:1) to receive cisplatin 25 mg/m² and gemcitabine 1000 mg/m² on day 1 and day 8/q3w with (arm A) or without panitumumab (arm B; 9 mg/kg BW, i.v q3w). The primary end-point was the evaluation of progression-free survival (PFS) at 6 months. Secondary end-points included objective response rate (ORR), overall survival (OS), and toxicity. In addition, a post hoc assessment of genetic alterations was performed. Finally, we performed a meta-analysis of trials with chemotherapy with and without EGFR antibodies.

Results

Sixty-two patients were randomised in arm A and 28 patients in arm B. Patients received 7 treatment cycles in median (1–35) with a median treatment duration of 4.7 months (141 days, 8–765). PFS rate at 6 months was 54% in patients treated with cisplatin/gemcitabine and panitumumab but was 73% in patients treated with cisplatin/gemcitabine without antibody, respectively. Secondary end-points were an ORR of 45% in treatment arm A compared with 39% receiving treatment B and a median OS of 12.8 months (arm A) and of 20.1 months (arm B), respectively. In contrast to the p53-status, genetic alterations in IDH1/2 were linked to a high response after chemotherapy and prolonged survival. In accordance with our results, the meta-analysis of 12 trials did not reveal a survival advantage for patients treated with EGFR antibodies compared with chemotherapy alone.

Conclusions

Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. Genetic profiling should be included in CCA trials to identify and validate predictive and prognostic biomarkers.