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K. Yoh
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MINI 15 - Chemotherapy Developments for Lung Cancer (ID 128)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Crinò, C.P. Belani
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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MINI15.08 - A Phase II Study of Pemetrexed plus Carboplatin Followed by Maintenance Pemetrexed in Elderly Patients with Advanced Non-Squamous NSCLC (ID 2453)
17:25 - 17:30 | Author(s): K. Yoh
- Abstract
- Presentation
Background:
Non-small-cell lung cancer (NSCLC) accounts for >80% of all lung cancers, and the risk of lung cancer clearly increases with advancing age. Because of the progressive aging of population, the number of elderly patients with NSCLC is increasing and the desease is becoming an increasing public health problem worldwide. We previously reported a phase I study that recommended a dose of carboplatin (Cb, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m[2]) for elderly (≥75-years-old) patients with non-squamous NSCLC. Furthermore, PEM maintenance therapy, following the combination therapy, was also found to be well tolerated. Therefore, we conducted a multicenter phase II trial to evaluated the efficacy and safety of Cb (area under the curve = 5) plus PEM (500 mg/m[2]) followed by maintenance PEM for elderly (≥75-years-old) patients with non-squamous NSCLC.
Methods:
Treated patients received 4 courses of Cb plus PEM, followed by maintenance PEM, without showing disease progression or severe toxicities. The primary endpoint was the 1-year overall survival (OS) rate, and the secondary endpoints were OS, progression free survival (PFS), response rate (RR), and safety.
Results:
Thirty four patients were enrolled between June 2012 and May 2013. All patients had an ECOG performance status 0 or 1, and adenocarcinoma. The median patient age was 77 years (75-84 years). Twenty four patients were male and ten patients were female. Three patients harbored activating epidermal growth factor recepter mutation (exon19 or 21). The median observation time was 22.7 months. In clinical outcome, the overall RR was 41.2%, and the disease control rate was 85.3%. No patient showed a complete response, 14 showed partial responses, 15 showed stable disease, 4 showed disease progression, and 1 was not evaluated. The maintenance therapy rate was 58.8%. The median PFS for all patients was 5.7 months (95% confidence interval, 3.3–8.5 months), whereas the median OS was 20.5 months (95% confidence interval, 7.8–25.4 months). The 1-year OS rate was 58.0%. In adverse events (total phase of this study), hematological adverse events ≥grade 3 were leucopenia (in 23.5% of patients), neutropenia (55.9%), anemia (35.3%), and thrombocytopenia (20.6%), and major non-hematological adverse events ≥grade 3 were febrile neutropenia (in 8.8% of patients), increased levels of aminotransferase (5.9%), infection (23.5%), and anorexia/fatigue (5.9%). There was 1 treatment-related death due to interstitial lung disease.
Conclusion:
The combination of Cb plus PEM followed by maintenance PEM was effective and reasonably well tolerated in chemotherapy-naïve elderly (≥75-years-old) patients with non-squamous NSCLC. This data was promising and valuable to conduct the phase III study compared with docetaxel (DOC) monotherapy in the first-line setting. Now, the phase III trial compared Cb plus PEM followed by maintenance PEM with DOC for chemotherapy-naïve elderly (≥75-years-old) patients with non-squamous NSCLC (JCOG1210/WJOG7813L: UMIN000011460) is ongoing and the result is warranted. Clinical trial information: UMIN000004810
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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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P1.01-022 - Radiologic Features of Advanced ALK-Rearranged Lung Cancer (ID 995)
09:30 - 09:30 | Author(s): K. Yoh
- Abstract
Background:
Reportedly, the radiologic features of most primary resectable lung cancers harboring an anaplastic lymphoma kinase (ALK)-fusion do not exhibit a ground-glass opacity (GGO) component when viewed using CT. However, little is known about the features of advanced ALK-rearranged lung cancer.
Methods:
The radiologic features of 21 advanced ALK-positive lung cancers treated at the National Cancer Center Hospital East between January 2012 and June 2014 were retrospectively investigated. ALK-fusion was confirmed using IHC and FISH or RT-PCR methods. The primary tumor’s diameter and characteristics (i.e., presence of a GGO component, notch, spiculation, and pleural indentation) as viewed using CT and the SUVmax observed using PET before treatment were evaluated. The radiologic features of 181 EGFR/ALK-negative non-sq NSCLCs treated during the same period were also evaluated as a control group. In addition, sites of distant metastases were evaluated.
Results:
The median age of patients with ALK-positive lung cancer was 58 years (range, 25-83 years). Of the 21 patients, 8 (39%) were female and 11 (52%) were never-smokers. The proportion of primary tumors smaller than 3 cm was significantly higher among the ALK-positive tumors than among the EGFR/ALK-negative tumors (48% vs. 21%, P = 0.01). Notches (71% vs. 41%, P = 0.01) and pleural indentations (81% vs. 55%, P = 0.03) were significantly more common among the ALK-positive tumors than among the EGFR/ALK-negative tumors. No significant differences in peripheral GGO (4.8% vs. 6.1%, P = 1.00) and spiculation (71.4% vs. 54.7%, P = 0.17) were observed. The median SUVmax values of the primary tumors were not significantly different (9.33 [range 4.56-28.81] vs. 10.54 [range 1.20-38.18], P = 0.91). Regarding the sites of distant metastases, liver (33% vs. 8%, P < 0.03) and pleural dissemination (48% vs. 24%, P = 0.03) were more frequent among patients with ALK-positive tumors than among patients with EGFR/ALK-negative tumors.
Conclusion:
We identified the radiologic features of advanced ALK-positive lung cancer, which include smaller-sized primary tumors and higher frequencies of notch and pleural indentation, compared with EGFR/ALK-negative tumors. These findings might be useful for the selection of patients with advanced ALK-positive lung cancer.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-064 - Microenvironmental Factor of Primary Lung Adenocarcinoma Which Predicts the Effectiveness of Chemotherapy in Patients with Recurrences (ID 815)
09:30 - 09:30 | Author(s): K. Yoh
- Abstract
Background:
The influence of microenvironmental factors on the effectiveness of chemotherapy is being increasingly recognized. Stromal cells in cancer tissue, such as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), have been shown to influence tumor progression. The associations of CD204-positive cells, which represent an M2 phenotype of TAMs, and podoplanin-positive CAFs, which represent a subpopulation of CAFs with a tumor-promoting phenotype, with a poor prognosis have been identified in patients with lung adenocarcinoma, but whether these associations are involved in the response to chemotherapy remains unknown. The purpose of this study was to investigate the relationships between cancer cell and stromal cell phenotypes in primary tumors and the progression-free survival (PFS) of recurrent lung cancer patients who received platinum-based chemotherapy.
Methods:
We retrospectively analyzed 87 postoperative recurrent lung adenocarcinoma patients treated with platinum-based chemotherapy. The expressions of drug resistance-related proteins including BCRP, Ezrin and ALDH1 in cancer cells, the number of CD204-positive TAMs, and the presence of podoplanin-positive CAFs in the primary tumor were examined. The relationships between the immunohistochemical staining results of primary tumors and the PFS after receiving chemotherapy were also analyzed.
Results:
Among the clinicopathological factors of primary tumors, only an advanced pathological stage was significantly associated with a shorter PFS. As for immunohistochemical staining, no significant relationships were found between the PFS and the expression of BCRP, Ezrin, or ALDH1. The number of CD204-positive TAMs was not associated with the PFS. The presence of podoplanin-positive CAFs, identified in thirty (34%) of 87 samples, was significantly associated with a shorter PFS (median PFS: 5.1 vs. 7.8 months, P=0.028), but was not significantly associated with a shorter overall survival (median survival time: 18.1 vs. 23.7 months, P=0.156). A multivariate analysis revealed a tendency of podoplanin-positive CAFs to be correlated with a shorter PFS (P=0.087).
Conclusion:
The presence of podoplanin-positive CAFs in the primary tumor could be a predictor of a shorter PFS in recurrent lung adenocarcinoma patients who received chemotherapy. These findings suggest that stromal-cell derived factors should be incorporated into predictions of the effectiveness of chemotherapy.
