Youjin Kim

Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01)

Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small‐molecule, triple‐receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC.

Pazopanib monotherapy in the treatment of pretreated, metastatic uterine sarcoma: a single-center retrospective study

Objective In the treatment of metastatic soft tissue sarcoma (STS), pazopanib is considered a standard treatment after failure of chemotherapy. We retrospectively investigated outcomes of pazopanib in patients with metastatic uterine STS. Methods A retrospective study was performed on 35 consecutive patients with uterine STS treated with oral pazopanib 800 mg daily as salvage therapy for metastatic disease between September 2013 and December 2015. Endpoints included response rate, survival, and safety. Results Among 35 patients, 27 (77%) had a histologic diagnosis of leiomyosarcoma (LMS) and the median age was 57 years (range, 36–70). Median number of metastatic sites was one (range, 1–5) with lung as the most frequently involved site. Pazopanib was generally well-tolerated: the major hematologic toxicity was grade 1/2 anemia (14%). Among the non-hematologic toxicities, grade 1/2 stomatitis was most commonly observed (22%), followed by fatigue and hypertension. Objective response and stable disease were observed in 10 (29%) and 11 (31%) patients, respectively. However, most cases of clinical response were observed in patients with LMS: 33% for LMS, 20% for undifferentiated pleomorphic sarcoma, and 0% for endometrial stromal sarcoma. Median progression-free and overall survivals were 5.8 months (95% confidence interval [CI]=3.6–8.1) and 20.0 months (95% CI=11.6–28.4), respectively. Conclusion In this “real-world” retrospective study, salvage therapy with pazopanib demonstrated clinically relevant efficacy and tolerability in unselected patients with uterine STS. Although it is encouraging that outcomes for Korean patients with uterine STS were similar to those reported in the phase III trial, the clinical benefit was limited to LMS.

Continuation of gefitinib beyond progression in patients with EGFR mutation-positive non-small-cell lung cancer: A phase II single-arm trial

OBJECTIVESnSeveral studies have demonstrated the promise of continuation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) beyond progression in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). The aim of the present study is to clarify the efficacy of continuation of gefitinib in patients with NSCLC beyond progression.nnnMATERIALS AND METHODSnA total of 50 patients with EGFR-mutant NSCLC who progressed based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria during gefitinib treatment were eligible. The primary endpoint was progression-free survival-2 (PFS2; time from first gefitinib dose to off-gefitinib progression). Secondary endpoints were PFS1 (time from first gefitinib dose to RECIST 1.1 progression); the difference between PFS2 and PFS1 (PFS2-PFS1); overall survival (OS); and safety. Patients received gefitinib 250u2009mg/d orally until symptomatic progression or at the investigators discretion.nnnRESULTSnBetween January 2016 and March 2017, 50 patients were enrolled in this study. One patient withdrew consent, leaving a total of 49 patients to be evaluated. The median PFS2-PFS1 was 5.1 months (95% CI, 2.5-7.8), and the median PFS2 was 27.7 months (95% CI, 21.6-33.9). Twelve patients (24.4%) continued gefitinib therapy for 14 months (median value, range 7.2-20.3 months) after RECIST 1.1 progression. The median OS was not reached. Patients were classified by the characteristics of progression at the time of enrollment. PFS2-PFS1 was significantly shorter in patients with pleural metastasis or pleural effusion compared with the other types of progression (1.8 months vs. 7.1 months, p-valueu2009=u20090.005).nnnCONCLUSIONnIn patients with EGFR-mutant NSCLC who experience progression, it is beneficial to maintain gefitinib treatment with local treatment such as radiotherapy until symptomatic progression. However, in patients with pleural metastasis or effusion, continuation of gefitinib beyond progression should be carefully determined on a case by case basis.

Efficacy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in patients with advanced pulmonary pleomorphic carcinoma

OBJECTIVESnPulmonary pleomorphic carcinoma (PC) is a rare type of lung tumor with a dismal prognosis. There is no consensus on a chemotherapy regimen for PC, and conventional platinum-based chemotherapy has been associated with disappointing response rates and PFS. In searches for a new regimen, the sarcomatoid (spindle or giant cell) component has been assumed to be susceptible to chemotherapy used for soft tissue sarcoma.nnnMATERIALS AND METHODSnThe medical records of 17 patients who received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for advanced PC between January 2010 and February 2017 were retrospectively analyzed for clinicopathological features and outcomes.nnnRESULTS AND CONCLUSIONnThe median age was 59 years. Sixteen patients were male, and only one patient had never smoked. Six patients achieved partial response to MAID, leading to an objective response rate of 35%. The median PFS was 2.8 months, and the median OS was 8.7 months. Hematologic toxicity-related adverse events were the most frequent, which comprised grade 3-4 anemia in 35% of patients, neutropenia in 47%, thrombocytopenia in 24%, and febrile neutropenia in 29%. No febrile neutropenia was reported in patients who received 5-day granulocyte-colony stimulating factor (G-CSF) prophylaxis. Most adverse events resolved without complications, except for one death due to sepsis. MAID is an effective, and possibly important, regimen for PC. MAID could be more safely used in clinical practice with appropriate dose modifications and G-CSF primary prophylaxis according to patients status.

Transient Asymptomatic Pulmonary Opacities During Osimertinib Treatment and its Clinical Implication

Introduction: Osimertinib is an oral, potent, irreversible third‐generation EGFR tyrosine kinase inhibitor approved for the treatment of T790M‐positive NSCLC patients who failed first‐ or second‐generation EGFR tyrosine kinase inhibitors. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1% to 3% of patients. Recently, a relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs), which are different from ILD, has been described. However, its clinical implication has not been fully determined yet. Methods: We retrospectively analyzed 74 EGFR T790M mutant NSCLC patients treated with osimertinib. Serial computed tomographic findings were reviewed by a thoracic radiologist independently, and TAPO was classified according to its radiologic pattern. We also analyzed the correlation of TAPO with clinical outcomes. Results: Among 74 patients, TAPOs were found in 15 (20.3%). The median time to TAPO development was 24.0 weeks (range, 1 to 72 weeks) and the median duration of TAPO was 6.0 weeks (range, 5 to 24 weeks) during continued osimertinib treatment. The most common radiological patterns of TAPO include cryptogenic organizing pneumonia and/or simple eosinophilic pneumonia. There was no significant difference in patient characteristics between TAPO‐positive and ‐negative groups. The duration of exposure to osimertinib was significantly longer in TAPO‐positive than ‐negative groups (25.0 months versus 13.0 months, p = 0.009). The median progression‐free survival and the median overall survival was numerically longer in TAPO‐positive than ‐negative groups (22 months versus 15 months for progression‐free survival, p = 0.293; 37 months versus 24 months for overall survival, p = 0.059), respectively. Conclusions: TAPOs are frequently observed with osimertinib treatment and may be mistaken for isolated pulmonary progression or drug‐induced ILD. Given the lack of serious clinical deterioration, it is reasonable to continue osimertinib with regular computed tomographic–scan follow‐up. For further clinical validation of TAPOs, long‐term follow‐up and large studies are warranted.