Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • MD was the recipient of the Intergroupe Francophone

    2023-03-17

    MD was the recipient of the Intergroupe Francophone de Cancérologie Thoracique (IFCT) Alain Depierre Grant in 2014. JP was the recipient of the ARISTOT (Association de Recherche, d’Information Scientifique et Thérapeutique en Oncologie Thoracique) grant in 2016.
    Conflicts of interest statement AMF has received research funding from Pfizer. She has been reimbursed for travel, accommodation, and/or other expenses by ThermoFisher, Clinisciences, Astra-Zeneca, Novartis, Pfizer and Roche and has served as a consultant (advisory board) for Novartis. MD has received research funding from Novartis and Pfizer. He has been reimbursed for travel, accommodation, and/or other expenses by Novartis, Pfizer and Roche. He has served as a consultant (advisory board) for Pfizer.
    Acknowledgements
    Introduction Crizotinib was the first approved tyrosine kinase inhibitor (TKI) by the US Food and Drug Administration (FDA) in 2011 for the treatment of metastatic anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) [1]. Both ceritinib and alectinib have been approved for patients who have progressed on or are intolerant to crizotinib. Brigatinib is currently pending FDA priority review for its indication in the second-line setting. Other next-generational ALK inhibitors, including ensartinib and lorlatinib, are at various stages of development. The optimal sequential utilization of these TKIs remains a clinical challenge as no head-to-head comparison has been conducted via randomized trials. One proposed method is to identify secondary ALK resistant Phosphatase Inhibitor Cocktail (2 Tubes, 100X) sale (s) upon disease progression under TKI treatment and then select another TKI that may overcome the mutation (s) if found. For instance, I1171T has been shown to confer resistance to alectinib, which may be rescued by ceritinib [2], [3]. Conversely, if F1174V is discovered upon progression on ceritinib, alectinib poses a viable treatment option [2]. Currently, we rely on well documented clinical narratives to develop our understanding of the clinical activities of these ALK inhibitors against various resistance mutations. Here we report for the first time the novel T1151K ALK mutation in a patient with metastatic ALK-rearranged NSCLC who progressed on crizotinib and then ceritinib.
    Case description A 33 year-old Asian man, former smoker of 8.5 pack years, initially presented with abdominal pain and weight loss in April 2010 for which outside workup revealed stage IV adenocarcinoma of the lung involving brain, liver, and bone. After receiving gamma knife therapy for his brain lesion, he was treated with chemotherapy containing carboplatin and pemetrexed for 6 cycles followed by maintenance pemetrexed for approximately 3 years until September 2013 when an MRI of the brain showed new brain metastases. A repeat biopsy of a lung mass in February 2014 detected an echinoderm microtubule-associated protein-like 4 (EML4)-ALK translocation of variant 3a/b via polymerase chain reaction performed by a commercial laboratory. Chemotherapy was switched to crizotinib, which was subsequently discontinued in October 2014 when the patient developed a new metastasis in the left parotid gland. He was treated with radiation and then placed on ceritinib at 750mg once daily, but the dose had to be reduced to 450mg once daily due to severe diarrhea. He experienced further disease progression with scans showing an enlarging lung mass in June 2016. At this point, he presented to our clinic to explore clinical trial options. Tissue obtained from another biopsy of this enlarging lung mass was sent to Foundation Medicine (Cambridge, MA, USA) for comprehensive genomic profiling (CGP), which confirmed the original ALK rearrangement. In addition, it revealed a novel ALK point mutation T1151K, resulting from a C>A nucleotide change observed in 30.0% of reads. He was enrolled onto another ALK inhibitor trial and has been doing well since.