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Clinical Trial
. 2021 Jun;17(3):264-272.
doi: 10.1111/ajco.13455. Epub 2020 Sep 7.

Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study

Takashi Nakano  1   2 , Kozo Kuribayashi  2 , Masashi Kondo  3 , Masahiro Morise  3 , Yuji Tada  4 , Katsuya Hirano  5 , Morihiko Hayashi  6 , Misa Tanaka  6 , Masataka Hirabayashi  5
Affiliations
Clinical Trial

Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study

Takashi Nakano et al. Asia Pac J Clin Oncol. 2021 Jun.

Abstract

Aims: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis and limited treatment options. Cisplatin plus pemetrexed is the only approved first-line treatment for patients with unresectable MPM. Recently, promising outcomes were observed with first-line bevacizumab combined with cisplatin/pemetrexed, leading to the recommendation of this regimen as a first-line treatment option for patients with MPM. Bevacizumab plus cisplatin/pemetrexed has been shown to be safe and effective in non-small cell lung cancer, however, there are no efficacy or safety data in Japanese patients with MPM treated with this regimen. We conducted a multicenter study to evaluate tolerability and safety for Japanese patients with chemotherapy-naïve, unresectable MPM.

Methods: Eligible patients (n = 7) received bevacizumab plus cisplatin/pemetrexed (up to six cycles), then single-agent bevacizumab until disease progression or onset of unacceptable adverse events (AEs), according to the 3+3 design analogy.

Results: One patient (14.3%) reported an AE (gastric ulcer) meeting tolerability criteria. All patients experienced gastrointestinal disorders, including nausea (grade 1/2 only, n = 6, 85.7%) and constipation (grade 1/2 only, n = 5, 71.4%). Five patients (71.4%) had grade 3 hypertension. Two patients discontinued treatment due to gastric ulcer (n = 1) and proteinuria (n = 1). At data cut-off, four patients had stable disease, two had partial response and one had non-complete response/non-progressive disease due to the absence of target lesions.

Conclusions: Bevacizumab plus cisplatin/pemetrexed then bevacizumab was well tolerated in Japanese patients with MPM.

Keywords: bevacizumab; cisplatin; malignant pleural mesothelioma; pemetrexed; safety.

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Conflict of interest statement

Takashi Nakano has received honoraria from MSD, Olympus Corporation, ISHIHARA Sangyo, KYORIN Pharmaceutical, Nippon Boehringer Ingelheim and ONO Pharmaceutical; acted in a consulting or advisory role for Nippon Boehringer Ingelheim; and reports personal fees from Cancer and Chemotherapy Publishers, Ishiyaku Publishers, IGAKU‐SHOIN, Elsevier Japan K.K., Asakura Publishing, Ministry of the Environment Japan and Amagasaki City, outside the submitted work. Kozo Kuribayashi has received honoraria from AstraZeneca, Astellas Pharma, Boehringer Ingelheim, Chugai Pharmaceutical, Kyowa Hakko Kirin, KYORIN Pharmaceutical, Meiji‐Seika‐Pharma, Novartis, Ono Pharmaceutical and Taiho Pharmaceutical. Masashi Kondo has received honoraria from Eli Lilly, MSD, Chugai Pharmaceutical, Pfizer, Novartis, AstraZeneca, Nippon Boehringer Ingelheim, Taiho Pharmaceutical and Kyowa Hakko Kirin. Masahiro Morise has received honoraria from Chugai Pharmaceutical, Eli Lilly Japan K.K., Ono Pharmaceutical, Bristol‐Myers Squibb, Pfizer, AstraZeneca, Boehringer Ingelheim, Merck Serono and Novartis. Yuji Tada has received honoraria from Chugai Pharmaceutical. Katsuya Hirano reports personal fees from AstraZeneca K.K., Chugai Pharmaceutical, Eli Lilly, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical and Novartis, outside the submitted work. Morihiko Hayashi and Misa Tanaka are employees of Chugai Pharmaceutical, and Misa Tanaka owns stock in Chugai Pharmaceutical. Masataka Hirabayashi has received honoraria from AstraZeneca K.K., Ono Pharmaceutical, KYORIN Pharmaceutical, Taiho Pharmaceutical, MSD, Chugai Pharmaceutical, Pfizer, Boehringer Ingelheim and Eli Lilly.

Figures

FIGURE 1
FIGURE 1
Study design
FIGURE 2
FIGURE 2
Treatment exposure. †, Cisplatin was replaced with carboplatin for Cycles 5 and 6. ‡, Ongoing
FIGURE 3
FIGURE 3
Patient case: Computed tomography scan after Cycle 7 in a 47‐year‐old, female patient who was diagnosed with stage III MPM, and experienced a partial response after receiving treatment without dose modification, other than cisplatin at Cycle 6, when treatment with cisplatin was discontinued mid‐treatment due to the occurrence of a systemic rash (patient #5)
See this image and copyright information in PMC

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