Junji Koyama

Efficacy of bevacizumab and erlotinib combination for leptomeningeal carcinomatosis after failure of erlotinib

In patients with non-small-cell lung cancer harboring an epithelial growth factor receptor (EGFR) active mutation, central nervous system progression after a response to EGFR tyrosine kinase inhibitors is frequent. Central nervous system metastasis, especially leptomeningeal carcinomatosis (LMC), is a serious complication and no standard treatment has been established for LMC. Here, we report two cases in which the addition of bevacizumab to erlotinib enhanced the efficacy against LMC; as a result, radiographic abnormalities decreased markedly and symptoms were well controlled. This combination treatment may be useful to treat LMC in patients with EGFR-positive non-small-cell lung cancer.

High ratio of T790M to EGFR activating mutations correlate with the osimertinib response in non-small-cell lung cancer

OBJECTIVESnOsimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that can overcome resistance due to the Thr790Met (T790M) mutation. However, osimertinib occasionally shows limited efficacy in a small population of patients. We investigated the correlation between the ratio of T790M to EGFR activating mutation and the response to osimertinib.nnnMATERIALS AND METHODSnBetween April 2016 and April 2017, 44 patients started osimertinib therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. We performed EGFR mutation analysis of cytological samples from 33 patients using droplet digital PCR. We calculated the ratio of T790M to EGFR activating mutations and correlated it with the systemic response to osimertinib.nnnRESULTSnIn tumors from the 33 patients, the average ratio of T790M to EGFR activating mutations was 0.420. Twenty-one of the 33 patients had tumors with a T790M ratio of ≥0.4. The osimertinib response rate was significantly higher (92.3%) in patients with a T790M ratio of ≥0.4 than in those with a T790M ratio of <0.4 (52.6%; pu202f=u202f0.0237). We examined the correlation between the T790M ratio and the tumor reduction rate and obtained a coefficient of ru202f=u202f0.417 (pu202f=u202f0.0175). In patients with a T790M ratio of ≥0.4, the median progression-free survival was 355u202fdays, which was longer, but not significant, than that in patients with a T790M ratio of <0.4 (median: 264u202fdays). In patients with a T790M ratio of ≥0.4, the median treatment duration from first-line therapy onward was 931u202fdays, which was significantly longer than that in patients with a T790M ratio of <0.4 (median, 567.5u202fdays) (pu202f=u202f0.044).nnnCONCLUSIONnThe T790M ratio to EGFR activating mutation in tumor may correlate with the response to osimertinib, and patients with a higher T790M ratio have a longer treatment history.

Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene

Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors.

EGFR T790M mutation after chemotherapy for small cell lung cancer transformation of EGFR-positive non-small cell lung cancer

In non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation, 50%–65% of cases acquire resistance after treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) because of an EGFR T790M point mutation and 3%–14% of these cases transformed to small cell lung cancer (SCLC). Generally, the EGFR T790M secondary mutation develops with ongoing ATP competitive inhibition. We present a case of a 76-year-old woman with lung adenocarcinoma harboring an EGFR-L858R mutation who received first-line gefitinib and developed SCLC transformation. She was administered several chemotherapy agents, including a platinum doublet. The primary lesion that showed SCLC transformation had reconverted to adenocarcinoma with EGFR L858R and T790M mutations at the time of a second re-biopsy. Therefore, she was administered osimertinib, which resulted in clinical remission. This case suggested that serial biopsies are necessary even after SCLC transformation.

Characterization of Computed Tomography Imaging of Rearranged During Transfection-rearranged Lung Cancer

Micro‐Abstract: Because rearranged during transfection (RET)‐rearranged non–small‐cell lung cancer (NSCLC) is rare, clarifying the computed tomography (CT) imaging characteristics is crucial. In 21 cases of advanced RET‐rearranged NSCLC, the CT imaging characteristics revealed relatively small and solid primary lesions without air bronchogram or cavitation, located as peripheral lung lesions, frequently disseminated to the pleura. These findings could help to better understand the progression pattern of RET‐rearranged NSCLC. Background: Rearranged during transfection (RET)‐rearranged non–small‐cell lung cancer (NSCLC) is relatively rare and the clinical and computed tomography (CT) image characteristics of patients with an advanced disease stage have not been well documented. Patients and Methods: We identified patients with advanced‐stage RET‐rearranged NSCLC treated in the Cancer Institute Hospital, Japanese Foundation for Cancer Research, and analyzed the clinical and CT imaging characteristics. Results: In 21 patients with advanced RET‐rearranged NSCLC, RET rearrangements were identified using fluorescence in situ hybridization and/or reverse transcriptase‐polymerase chain reaction. The fusion partner genes were identified as KIF5B (57%), CCDC6 (19%), and unknown (24%). CT imaging showed that 12 primary lesions (92%) were peripherally located and all were solid tumors without ground‐glass, air bronchograms, or cavitation. The median size of the primary lesions was 30 mm (range, 12–63 mm). Of the 18 patients with CT images before initial chemotherapy, 12 (67%) showed an absence of lymphadenopathy. Distant metastasis included 13 with pleural dissemination (72%), 10 with lung metastasis (56%), 8 with bone metastasis (44%), and 2 with brain metastasis (11%). Conclusion: Advanced RET‐rearranged NSCLC manifested as a relatively small and peripherally located solid primary lesion with or without small solitary lymphadenopathy. Pleural dissemination was frequently observed.