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M. Higuchi
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ORAL 10 - SCLC (ID 98)
- Event: WCLC 2015
- Type: Oral Session
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:C. Faivre-Finn, P. Lara Jr.
- Coordinates: 9/07/2015, 10:45 - 12:15, 605+607
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ORAL10.07 - Clinical and Molecular Profiling of Surgically Resected Small Cell Lung Cancer (ID 2235)
12:10 - 12:21 | Author(s): M. Higuchi
- Abstract
- Presentation
Background:
NCCN, ACCP and Japanese guidelines suggest surgery for patients with c-stage I small-cell lung cancer (SCLC), while ESMO guidelines recommend surgery for patients with c-stage II (T1,2 N0,1). In addition, the clinical impact of surgery with other variables on patients with early-stage SCLC has yet to be determined. Therefore, clarification of the clinical profile of surgically resected SCLC is required. Suppression of MED12, a subunit of the transcriptional MEDIATOR complex in conjunction with cell surface expression of TGF-βRII was reported to be correlated with the resistance mechanism of EGFR-TKIs, crizotinib, and chemotherapy. Few investigators examined the expression profile of MED12 as well as receptor tyrosine kinases in SCLC. A next-generation sequencing (NGS) system is a novel technology for sequencing genomes at high-throughput and with great accuracy using deep sequencing. It has been instrumental for translational study integrating the detection of genetic alteration analysis into the better understanding of tumor biology, as well as treatment of various types of cancers. Recently, SOX-2 amplification, histone modification, and genetic alterations in the PI3K/AKT/mTOR pathway were reported to be potential targets of SCLC using NGS through whole exon analysis. However, further investigation is needed for the personalized treatment of SCLC. We updated the molecular data using NGS, which had been presented at ESMO 2014 (abstract ID: 5724).
Methods:
We reviewed the clinical courses of 156 patients with SCLC who had undergone surgery at 17 institutes from January 2003 through January 2013. One hundred twenty-five formalin-fixed paraffin-embedded tissue samples were subjected to immunohistochemistry using seven antibodies (MED12 and TGF-βRII, ALK, c-Met, EGFR, c-kit, and VEGFRII) and to NGS systems using MiSeq and TruSight Tumor Sequencing Panel (Illumina) loading 26 cancer-specific genes. (UMIN registration No. 000010116 /10117).
Results:
Median relapse-free survival and overall survival (OS) were 15.6 (95%CI=6.8-24.5) and 33.3 (20.9-45.8) months, respectively. Multivariate analysis revealed that OS was longer in patients without a history or presence of other types of cancer (HR: 0.545, 95%CI=0.335-0.887, p=0.014), with preoperative diagnosis (HR: 0.510, 95%CI=0.299-0.871, p=0.014), with c-stage II and under (HR: 0.288, 95%CI=0.154-0.541, p<0.001) and with prophylactic cranial irradiation (HR: 0.300, 95%CI=0.092-0.976, p=0.045). Of the 125 patients whose samples were available, MED12 and TGF-βRII were highly expressed in nucleus and cytoplasm, respectively in 92% and 55% of the samples. None of the tumors expressed ALK. There was no relationship between the expression of c-Met, EGFR, and VEGFRII and either of RFS or OS. Multivariate analysis demonstrated that high expression of c-kit in tumor is an independent factor for longer OS (HR=0.543, 95%CI: 0.310-0.953, p=0.033). Seventy-nine samples have been subjected to NGS. Three actionable gene mutations, EGFR (E746_A750del), KRAS (G12D), and AKT1 (E17K) were found.
Conclusion:
These results supported the ESMO guidelines for the management of early-stage SCLC, and indicated that presence or history of other types of cancer might be a major decisive factor for surgery. The results of immunohistochemistry using antibodies of selective molecules and NGS assist us in gaining a better understanding of the biology and treatment strategy of SCLC.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-051 - Efficiency of Nab-Paclitaxel as a Late Phase Chemotherapy for NSCLC (ID 238)
09:30 - 09:30 | Author(s): M. Higuchi
- Abstract
Background:
Nanoparticle albumin-bound (nab) paclitaxel is a biologically interactive nanoparticle, combining albumin with paclitaxel and has a better toxicity profile compared to solvent-based paclitaxel. Recently some studies are reported which show the efficacy of nab-paclitaxel as first line chemotherapy for non-small cell lung cancer (NSCLC), but rarely reported until today to elucidate the efficacy of nab-paclitaxel with carboplatin (CBDCA) as second or later phase chemotherapy for NSCLC. We here evaluate the efficiency and feasibility of nab-paclitaxel plus CBDCA as second or later phase chemotherapy in patients with recurrent or advanced NSCLC in this study.
Methods:
Twenty-five patients with recurrence after radical surgery for NSCLC and unresectable stage IIIB/IV NSCLC who had received previous chemotherapies were treated with nab-paclitaxel 70mg/m[2] intravenously on day1, 8, and 15 with CBDCA area under the concentration-time curve of 4 (AUC4) intravenously on day1, every 28 days. Progression-free (PFS) and overall survival (OS) rates were calculated by means of Kaplan-Meier analysis and statistical significance between the groups was analyzed by using log-rank tests. Disease control rates and toxicity were also evaluated. Disease response in all of the patients was monitored after two cycles of chemotherapy.
Results:
Of 25 patients who participated in this study, 9 were recurrent and 16 were advanced case. 13 were adenocarcinoma, 11 were squamous cell carcinoma and 1 was large cell carcinoma. 13 were performed as second line chemotherapy, 6 were as third line and 6 were forth or later line. EGFR mutation status was positive in 5 patients (20.0%) and they all received EGFR-TKI in their serial chemotherapy. One achieved complete response (CR), 7 reached a stage of partial responses (PR), 10 maintained stable disease (SD) and 7 suffered progressive diseases (PD). The overall response rate (ORR) was 32.0% and disease control rate (DCR) was 72.0%. The median PFS was 4.8 months and median OS was 29.0 months. Common treatment related adverse events were myelosuppression, baldness, peripheral neuropathy and gastrointestinal symptoms, most of which were grade 1 to 2. Grade 3-4 neutropenia was present in 6 patients (24.0%), thrombocytopenia and anemia in 2 patients (8.0%), respectively. No patients experienced grade 3-4 neuropathy. The need of a dose reduction was 26.9% because of toxicity, but there were no adverse effects of grade 5.
Conclusion:
Nab-paclitaxel plus CBDCA as second or later phase chemotherapy offers a small but significant survival benefits for the patients with recurrent and advanced NSCLC, and its adverse effects are tolerable. Further studies including prospective studies of this regimen are required.
