440P Phase III randomized trial comparing short-term infusion of
oxaliplatin and capecitabine (Xelox30) with chronomodulated
(Xelox30) in patients with advanced and/or metastatic colorectal
cancer
M.Q. Nafea, S.H. Mahmoud, N.M. Gado, Z.M. Abdel Hafeez, K.K-E. El-Ghonemy
Clinical Oncology (ASCOD), Ain Shams University Hospital - Faculty of Clinical Medicine
and Radiation Oncology, Cairo, Egypt
Background: Approximately 50% of patients diagnosed with colorectal cancer (CRC)
will develop metastatic disease (mCRC). Oxaliplatin in combination with Capecitabine
prolongs survival in patients with mCRC. Chronomodulation might reduce toxicity and
improve efficacy of this treatment strategy.
Methods: In this prospective phase III trial, 100 patients were randomized to receive:
Arm A (XELOX30) 30 min-infusion of oxaliplatin 130 mg/m2 on day 1 plus oral
Capecitabine at a total dose of 2000 mg/m2 daily with 50% of the dose in the
morning and 50% of the dose in the evening; Arm B (XELOX30 Chrono) oxaliplatin:
130 mg/m2 on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total
daily dose of 2000 mg/m2, 20% of the dose between 7 and 9 a.m. and 80% of the
dose between 6 and 8 p.m. for 14 days followed by one week rest. Six to eight cycles
were recommended unless progressive disease or unacceptable toxicity occurred.
Baseline radiological investigations: CT chest, PA (pelvi-abdominal) every 2 cycles for
response assessment, adverse events were graded in accordance with the Common
Terminology Criteria for Adverse events (v4.03, 2010).
Results: An overall objective response was observed in 48 patients (96%) for
(XELOX30 Chrono) versus 42 patients (84%) (XELOX30) (P¼ 0.12%) with non-signifi-
cant longer time to progression (PFS) for (XELOX30 Chrono) (P¼1). No significant
differences in the one year OS rates were observed between the two arms (87.5%
versus 100%), although marginal significance was observed with P value close to
significant level for (XELOX30 Chrono) (P ¼ 0.056). Toxicity assessment showed
grade II neuropathy was significantly more frequent in the XELOX30 group compared
to the XELOX30 Chrono group (P¼ 0.003%). Subgroup analysis of the treatment arms
revealed patients who died were significantly younger with more weight loss than
those who survived.
Conclusions: The chronomodulated XELOX regimen may reduce overall toxicity and
improve efficacy; longer follow up period may be required to confirm these results. A
30-minute infusion of oxaliplatin seems safe and did not increase the severity of
peripheral neuropathy.
Legal entity responsible for the study: The authors.
Funding: Has not received any funding.
Disclosure: All authors have declared no conflicts of interest.
https://doi.org/10.1016/j.annonc.2020.08.551
441P Evaluation of conversion therapy in patients undergoing secondary
resection of metastases in curative intent within the FIRE-3 (AIO
KRK-0306) study
J.C. von Einem1
, V. Heinemann2
, D.P. Modest1
, A. Stahler3
, L. Miller-Phillips4
,
L. Fischer von Weikersthal5
, T. Decker6
, A. Kiani7
, U. Vehling-Kaiser8
, S-E. Al-Batran9
,
C. Kahl10
, G. Seipelt11
, F. Kullmann12
, W. Scheithauer13
, A. Jung14
, T. Kirchner15
,
S. Stintzing16
1
Medical Department, Divison of Hematology, Oncology and Tumor Immunology
(CCM), Charité - Universitätsmedizin Berlin, Berlin, Germany; 2
Comprehensive Cancer
Center Munich Department of Medicine III, Ludwig Maximilian University of
Munich, Munich, Germany; 3
Department of Internal Medicine III, LMU - Ludwig
Maximilians University - Grosshadern, Munich, Germany; 4
Department of Medicine III,
Ludwig Maximilians University - Grosshadern, Munich, Germany; 5
Onkologie,
Gesundheitszentrum St. Marien GmbH, Amberg, Germany; 6
Hematology Oncology,
Onkologie Hamatologie Ravensburg, Ravensburg, Germany; 7
Oncology, Klinikum
Bayreuth, Bayreuth, Bavaria, Germany; 8
Oncology, Praxis Dr. Vehling-Kaiser, Landshut,
Germany; 9
Institute of Clinical Cancer Research, Nordwest-Krankenhaus, Frankfurt am
Main, Germany; 10
Oncology, Klinikum Magdeburg, Magdeburg, Germany; 11
Onkolo-
gische Schwerpunktpraxis, Onkologische Schwerpunktpraxis Bad Soden, Bad Soden,
Germany; 12
Medizinische Klinik I, Klinikum Weiden, Weiden In Der Oberpfalz, Ger-
many; 13
Int.Med.I CCC Department, Vienna General Hospital (AKH) - Medizinische
Universität Wien, Vienna, Austria; 14
Pathology, Pathologisches Institut-LMU München,
Munich, Germany; 15
Pathology, LMU - Ludwig Maximilians University - Grosshadern,
Munich, Germany; 16
Medical Department, Division of Oncology and Hematolgogy,
Charité - Universitätsmedizin Berlin, Berlin, Germany
Background: FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or
bevacizumab in RAS wild-type mCRC patients. Here, we investigated the subgroup of
patients that underwent secondary mestastasectomy in curative intent to explore the
relevance of conversion treatment based on anti-EGFR- versus anti-VEGF directed
antibodies.
Methods: Patients who underwent resection in curative intent defined as reason for
end of study treatment and bearing a RAS wild-type tumor within the FIRE-3 study
were investigated. For those a retrospective, unplanned analysis was done comparing
cetuximab and bevacizumab treated patients. Median survival times were estimated
using the Kaplan-Meier method and compared using the logrank test.
Results: Within the extended RAS wild-type population of 400 patients, 25 out of 199
patients treated with cetuximab and 26 out of 201 patients treated with bevacizumab
were resected in curative intent. Median PFS was 10.9 months (95% CI: 6.4 e 15.5
months) in the cetuximab arm and 12.8 months (95% CI: 11.9 e 13.6 months) in the
bevacizumab-arm (logrank P ¼ 0.95). Median OS reached 56.9 months (95% CI: 53.7
e 60.0 months) and 38.1 months (95% CI: 11.9 e 64.3 months), respectively (P¼
0.19). Overall survival after resection was 40.7 months (95% CI: 16.7 e 64.7 months)
in the cetuximab arm and 19.4 months (95% CI: 16.0 - 22.2 months) in bevacizumab
treated patients (P¼ 0.19).
Conclusions: Patients undergoing secondary resection in curative intent within the
FIRE-3 trial had a numerically longer postsurgical survival and longer overall survival
when treated with FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab.
Clinical trial identification: NCT00433927.
Legal entity responsible for the study: Volker Heinemann.
Funding: Merck KGaA, Darmstadt, Germany.
Disclosure: All authors have declared no conflicts of interest.
https://doi.org/10.1016/j.annonc.2020.08.552
442P Camrelizumab combined with apatinib in the treatment of patients
with advanced gastric cancer and colorectal cancer: One-arm
exploratory clinical trial
L. Xiao, Y. Zhang, Q. Lin
Oncology, Zhongshan Hospital Xiamen University, Xiamen, China
Background: Camrelizumab is a selective, humanized, high-affinity immunoglobulin
G4/k monoclonal antibody against PD-1. Apatinib is a novel small-molecule TKI that
exerts its antitumour effect by targeting VEGFR-2. Anti-angiogenic agents can
modulate the immunosuppressive tumour microenvironment, which contributes to
resistance to anti-PD-1/PD-L1 treatment. This study assessed the safety and efficacy
of camrelizumab and apatinib as combination therapy in patients with relapsed /
metastatic gastric cancer (GC) and colorectal cancer (CRC).
Methods: We enrolled patients with previously treated (at least 2 lines of systemic
therapy) advanced GC or CRC. ECOG PS 0-1, and no prior immuno-oncology (IO)
therapy. Eligible patients were planned to receive camrelizumab 200 mg day1 and 15,
apatinib 250 mg day1-28, every 4 weeks until disease progression or intolerable
toxicity. The primary endpoint was investigator-assessed objective response rate
(ORR). Secondary endpoint was progression free survival (PFS), overall survival (OS),
safety, tolerability and disease control rate (DCR).
Results: Until April 2020, 20 CRC patients and 15 GC patients were enrolled in the
study. The median number of prior treatment lines was 3 (range 3-5). Liver metas-
tases were observed in 27 (77.1%) patients, 7 (20.0%) had lung metastases, 8 (22.9%)
had abdominal lymph node metastases, and 10 (28.6%) had metastases at other sites.
16 (80.0%) CRC patients had received prior treatment with anti-angiogenic agents. In
the GC cohort ,3 patients had a partial response (PR), 8 had stable disease (SD) and 4
had progressive disease (PD). ORR in this cohort was 20.0% and DCR was 80.0%. In
the CRC cohort, 6 patients had PR, 10 had SD and 4 had PD. ORR was 30.0 % and DCR
was 80.0%. Median estimates for PFS and OS for both cohorts were not reached. In all
patients, grade 3 treatment-related adverse events (TRAEs) included neutrophil
decrease (2.3%, increased ALT (13.3%), increased AST (13.3%), fatigue (5.7%),
increased blood bilirubin (6.7%), hypertension (11.4%,), and proteinuria (6.7%). None
of the TRAEs were fatal.
Conclusions: Camrelizumab and low-dose apatinib combination therapy demon-
strated manageable toxicity and might offer a new promising choice for those pa-
tients with GC and CRC who have failed standard therapy.
Clinical trial identification: NCT04067986.
Legal entity responsible for the study: The authors.
Funding: Jiangsu Hengrui Medicine Co. (Shanghai) Ltd.
Disclosure: All authors have declared no conflicts of interest.
https://doi.org/10.1016/j.annonc.2020.08.553
abstracts Annals of Oncology
Volume 31 - Issue S4 - 2020 S429