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1.
Chun A. Changou Her-Shyong Shiah Li-Tzong Chen Servina Liu Frank Luh Shwu-Huey Liu Yung-Chi Cheng Yun Yen 《The oncologist》2021,26(3):e367-e373
Lessons Learned
- A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies.
- This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.
2.
Thomas J. George Alison M. Ivey Azka Ali Ji-Hyun Lee Yu Wang Karen C. Daily Brian H. Ramnaraign Sanda A. Tan Krista P. Terracina Thomas E. Read Long H. Dang Atif Iqbal 《The oncologist》2021,26(5):362-e724
Lessons Learned
- Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance.
- In this single‐arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression‐free survival of 6.2 months with an acceptable toxicity profile.
- This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC.
3.
Jennifer E. Amengual Jennifer K. Lue Helen Ma Renee Lichtenstein Bijal Shah Serge Cremers Simon Jones Ahmed Sawas 《The oncologist》2021,26(3):184-e366
Lessons Learned
- Oral selective HDAC6 inhibitors could allow for decreased toxicity compared to pan‐class inhibitors, and increased ease of use.
- ACY‐1215 is well tolerated and led to disease stabilization in 50% of patients treated on a twice‐daily dosing schedule.
- Rational drug combinations with ACY‐1215 improve efficacy in patients with lymphoma.
- Biomarkers such as XBP‐1 level or HDAC6‐score may improve patient selection.
4.
Her-Shyong Shiah Nai-Jung Chiang Chia-Chi Lin Chia-Jui Yen Hui-Jen Tsai Shang-Yin Wu Wu-Chou Su Kwang-Yu Chang Ching-Chiung Wang Jang-Yang Chang Li-Tzong Chen 《The oncologist》2021,26(4):e567-e579
Lessons Learned
- SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
- This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
- SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.
5.
Richard Kim Elaine Tan Emily Wang Amit Mahipal Dung-Tsa Chen Biwei Cao Fadzai Masawi Cindy Machado James Yu Dae Won Kim 《The oncologist》2020,25(12):e1893-e1899
Lessons Learned
- The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
- Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
- The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.
6.
Fei Xu Qiufan Zheng Wen Xia Quchang Ouyang Danmei Pang Zhongyu Yuan Yanxia Shi Roujun Peng Qianyi Lu Shusen Wang 《The oncologist》2021,26(5):e742-e748
Lessons Learned
- Fulvestrant 500 mg maintenance therapy showed a clinical benefit rate of 76% and median progression‐free survival of 16.1 months in patients who achieved objective responses or disease control after first‐line chemotherapy.
- Adverse events with fulvestrant maintenance therapy were consistent with the known safety profile of the drug.
7.
Xiao-Dong Jiao Ke Liu Mingyan Xu Guanzhen Yu Danni Liu Tanxiao Huang Bao-Dong Qin Ming Liu Ying Wu Yan Ling Jun Liu Xi He Liangzhe Wang Yingmei Li Shifu Chen Yuan-Sheng Zang 《The oncologist》2021,26(4):e524-e529
This article reports a case of advanced metastatic low‐grade sarcoma. The patient was diagnosed with an inoperable large (14 × 12 cm) lesion on his neck in September 2015 and underwent two ineffective chemotherapies in the following 4 months. Interestingly, although several pathologists could not agree on the histopathological diagnosis, the precise molecular pathological diagnosis was obtained using next‐generation sequencing (NGS) and finally brought excellent therapeutic effects. The patient was detected to have CARS‐ALK fusion by NGS and then was successfully treated with crizotinib orally. He received surgical resection of primary and metastatic lesions after tumor shrinkage. The combined treatment brought a durable response for 40 months. Although the tumor recurred in July 2019, the patient has been responding well to the second‐line ALK tyrosine kinase inhibitor alectinib to date. We performed whole genome sequencing on the patient''s primary, metastatic, and recurrent tumors and did comprehensive genomic analysis. Furthermore, our analysis results revealed that a whole genome duplication event might have happened during tumorigenesis of this case.Key Points
- To our best knowledge, this is the first report of a very successful treatment with first‐ and second‐line ALK tyrosine kinase inhibitors for CARS‐ALK fusion–positive metastatic low‐grade sarcoma.
- Molecular pathological result can guide precision treatment for sarcoma, even when the exact histopathology cannot be obtained.
- Multiple samples from this patient were analyzed using whole genome sequencing. Results provided detailed genomic characteristics and showed tumor evolution of this low‐grade sarcoma case.
- A whole genome duplication event might have happened during tumorigenesis of this low‐grade sarcoma case.
8.
Ghassan K. Abou-Alfa Robert Mayer Alan P. Venook Allison F. O'Neill Muhammad S. Beg Michael LaQuaglia Peter T. Kingham Rachel Kobos Olca Basturk Cameron Brennan Adam Yopp James J. Harding Stephen Leong John Crown Emir Hoti Gregory Leonard Michele Ly Mikaela Bradley Emily Valentino David Markowitz Alexander Zukiwski Ken Ren John D. Gordan 《The oncologist》2020,25(12):e1837-e1845
9.
ChiaChi Lin TsaiSheng Yang ChiaJui Yen Rebecca Cheng Junjun Liu Chiun Hsu 《The oncologist》2020,25(12)
Lessons Learned
- The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first‐line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated.
- Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC.
- Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC.
10.
Patients with non‐small cell lung cancer (NSCLC) containing ROS1 fusions can have a marked response to the ROS1‐targeted tyrosine kinase inhibitors (TKIs), such as crizotinib. Common resistance mechanisms of ROS1‐fusion targeted therapy are acquired mutations in ROS1. Along with the use of next‐generation sequencing in the clinical management of patients with NSCLC during sequential targeted therapy, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Besides acquired resistance mutations, bypass mechanisms of resistance to epidermal growth factor receptor (EGFR)‐TKI treatment are common in patients with EGFR mutations. Here we describe a patient with metastatic lung adenocarcinoma with CD74‐ROS1 fusion who initially responded to crizotinib and then developed resistance by the acquired mutation of D1228N in the MET kinase domain, which showed short‐term disease control for cabozantinib.Key Points
- The D1228N point mutation of MET is an acquired mutation for crizotinib resistance.
- The patient obtained short‐term clinical benefit from cabozantinib therapy after resistance to crizotinib.
- The clinical use of next‐generation sequencing could maximize the benefits of precision medicine in patients with cancer.
11.
Hironaga Satake Takeshi Kato Koji Oba Masahito Kotaka Yoshinori Kagawa Hisateru Yasui Masato Nakamura Takanori Watanabe Toshihiko Matsumoto Takayuki Kii Tetsuji Terazawa Akitaka Makiyama Nao Takano Mitsuru Yokota Yoshihiro Okita Koreatsu Matoba Hiroko Hasegawa Akihito Tsuji Yoshito Komatsu Takayuki Yoshino Kentaro Yamazaki Hideyuki Mishima Eiji Oki Naoki Nagata Junichi Sakamoto 《The oncologist》2020,25(12):e13443
Lessons Learned
- A biweekly TAS‐102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS‐102 plus BEV combination.
- Biweekly TAS‐102 plus BEV combination could reduce unnecessary dose reduction of TAS‐102, maintain higher doses, and possibly be effective even in cases without chemotherapy‐induced neutropenia (CIN).
- The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS‐102 plus BEV.
12.
Hidetoshi Hayashi Masakazu Ogura Takashi Niwa Toshihide Yokoyama Junko Tanizaki Tomohiro Ozaki Hiroshige Yoshioka Takayasu Kurata Yosuke Tamura Yasuhito Fujisaka Kaoru Tanaka Yoshikazu Hasegawa Keita Kudo Yasutaka Chiba Kazuhiko Nakagawa 《The oncologist》2021,26(1):19-e52
Lessons Learned
- The combination of cisplatin plus nab‐paclitaxel with concurrent thoracic radiotherapy in unresectable stage III non‐small cell lung cancer is a promising therapeutic strategy.
- Further investigation is warranted.
13.
Li Chu Yun Chen Qi Liu Fei Liang Shengping Wang Quan Liu Hui Yu Xianghua Wu Junhua Zhang Jiaying Deng Dashan Ai Zhengfei Zhu Yongzhan Nie Kuaile Zhao 《The oncologist》2021,26(6):e925-e935
Lessons Learned
- Apatinib has potential as an effective and safe second‐line or higher treatment for patients with chemotherapy‐refractory esophageal squamous cell carcinoma (ESCC).
- Clinical safety is of potential concern when administering apatinib to patients with uncontrolled esophageal lesions or severe invasion of trachea, bronchi, or major blood vessels.
- To the best of the authors'' knowledge, this is the first prospective phase II study to investigate apatinib for patients with chemotherapy‐refractory ESCC. Apatinib could provide an alternative option for ESCC after first‐line or higher therapy in carefully selected patients.
14.
Margaret E. Gatti-Mays Fatima H. Karzai Sanaz N. Soltani Alexandra Zimmer Jeffrey E. Green Min-Jung Lee Jane B. Trepel Akira Yuno Stanley Lipkowitz Jayakumar Nair Ann McCoy Jung-Min Lee 《The oncologist》2020,25(12):1013-e1824
Lessons Learned
- Monotherapy with prexasertib demonstrated modest activity in BRCA wild‐type, recurrent triple‐negative breast cancer, highlighting the unmet need for combination treatment strategies.
- Neutropenia, anemia, and thrombocytopenia are common with the use of prexasertib but are manageable with supportive care measures. Prophylactic use of granulocyte colony stimulating factor should be considered to avoid dose reductions or treatment delays.
- Pharmacodynamic studies showed prexasertib treatment induced DNA damage in peripheral immune cells.
15.
Juncheng Xuhong Xiaowei Qi Peng Tang Linjun Fan Li Chen Fan Zhang Xuanni Tan Wenting Yan Ling Zhong Cheng He Yan Liang Lin Ren Minghao Wang Yi Zhang Jun Jiang 《The oncologist》2020,25(12):e13546
Lessons Learned
- This is the first trial to explore the neoadjuvant therapy of pyrotinib in HER2‐positive operable and locally advanced breast cancer, in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab.
- Results primarily showed that pyrotinib in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab was effective and safe in HER2‐positive operable and locally advanced breast cancer.
- A subsequent randomized controlled trial is still warranted to confirm these results.
16.
Zhenhuan Zhao Yixue Wen Dongbiao Liao Jidong Miao Yan Gui Hongwei Cai Yang Chen Min Wei Qiang Jia Honggang Tian Mingqiang Sun Yu Zhang Gang Feng Xiaobo Du 《The oncologist》2020,25(12):e13492
Lessons Learned
- The efficacy of single‐agent chemotherapy was not significantly different from that of double‐agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma.
- Single‐agent concurrent chemoradiotherapy had lower gastrointestinal and hematologic toxicity.
- Overall survival and progression‐free survival were not significantly different between single‐ and double‐agent concurrent chemoradiotherapy.
17.
Dickran Kazandjian Alexander Dew Elizabeth Hill Elizabeth Gil Ramirez Candis Morrison Esther Mena Liza Lindenberg Constance Yuan Irina Maric Hao-Wei Wang Katherine Calvo Alina Dulau-Florea Joseph Roswarski Michael Emanuel Raul Braylan Baris Turkbey Peter Choyke Kevin Camphausen Maryalice Stetler-Stevenson Seth M. Steinberg William D. Figg Jennifer C. Jones 《The oncologist》2021,26(4):288-e541
Lessons Learned
- Despite the initial optimism for using immune checkpoint inhibition in the treatment of multiple myeloma, subsequent clinical studies have been disappointing.
- Preclinical studies have suggested that priming the immune system with various modalities in addition to checkpoint inhibition may overcome the relative T‐cell exhaustion or senescence; however, in this small data set, radiotherapy with checkpoint inhibition did not appear to activate the antitumor immune response.
18.
Kaname Nosaki Takeharu Yamanaka Akinobu Hamada Yoshimasa Shiraishi Taishi Harada Daisuke Himeji Takeshi Kitazaki Noriyuki Ebi Takayuki Shimose Takashi Seto Mitsuhiro Takenoyama Kenji Sugio 《The oncologist》2020,25(12):e13442
Lessons Learned
- This phase II trial evaluated the efficacy of erlotinib for patients with non‐small cell lung cancer with leptomeningeal metastasis.
- The 17 cerebrospinal fluid specimens that were available for epidermal growth factor receptor mutation analysis were all negative for the resistance‐conferring T790M mutation.
- The cytological objective clearance rate was 30.0% (95% confidence interval: 11.9%–54.3%). The median time to progression was 2.2 months.
- The rate of cerebrospinal fluid penetration among these patients was equivalent to those in previous reports regarding leptomeningeal metastasis.
19.
James J. Harding Robin K. Kelley Benjamin Tan Marinela Capanu Gian Kinh Do Jinru Shia Joanne F. Chou Christine S. Ferrer Chayma Boussayoud Kerri Muenkel Hooman Yarmohammadi Imane El Dika Danny N. Khalil Carmen Ruiz Mariam Rodriguez-Lee Peter Kuhn John Wilton Renuka Iyer Ghassan K. Abou-Alfa 《The oncologist》2020,25(12):e1825-e1836
Lessons Learned
- Androgen receptor as assessed by immunohistochemistry is expressed in a high proportion of patients with hepatocellular carcinoma (HCC).
- Enzalutamide at 160 mg orally daily is safe and tolerable in patients with advanced HCC but has no single‐agent antitumor activity.
- Enzalutamide, a CYP3A4 inducer, at a standard dose of 160 mg reduces the exposure of sorafenib, a CYP3A4 substrate.
- Enzalutamide and sorafenib is safe and tolerable in patients with advanced HCC, but the addition of enzalutamide to sorafenib did not enhance the antitumor activity of sorafenib.
20.
Tetsuji Terazawa Takeshi Kato Masahiro Goto Katsuya Ohta Shingo Noura Hironaga Satake Yoshinori Kagawa Hisato Kawakami Hiroko Hasegawa Kazuhiro Yanagihara Tatsushi Shingai Ken Nakata Masahito Kotaka Masayuki Hiraki Ken Konishi Shiro Nakae Daisuke Sakai Yukinori Kurokawa Toshio Shimokawa Taroh Satoh 《The oncologist》2021,26(1):17-e47
Lessons Learned
- Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
- It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.