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Y.H. Kim
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-005 - Phase 2 Study of Ceritinib in Patients with ALK+ NSCLC with Prior Alectinib Treatment in Japan: ASCEND-9 (ID 8417)
09:30 - 16:00 | Author(s): Y.H. Kim
- Abstract
Background:
ALK inhibitors are a standard of care for ALK-positive metastatic NSCLC and several ALK inhibitors are currently available. Alectinib is one of the recommended therapies as 1[st] line treatment for ALK-positive metastatic NSCLC in Japan based on robust progression-free survival (PFS) prolongation and favorable safety profile. However, even with treatment with alectinib, these cancers eventually progress after acquiring resistance against alectinib. Therefore, which drug should be chosen after alectinib is relevant clinical question. Recently, ceritinib, which is a highly selective oral ALK inhibitor, has demonstrated superior activity compared to chemotherapy in the 1[st] line setting for patients with ALK-positive metastatic NSCLC (ASCEND-4, Soria et al. Lancet 2017). It also showed clinically meaningful benefit in patients who failed to prior ALK inhibitor treatment including alectinib (Nishio et al. J Thorac Oncol 2015). In this study, we tried to evaluate efficacy and safety of ceritinib in ALK-positive metastatic NSCLC patients who progressed on alectinib treatment.
Method:
ASCEND-9 (NCT02450903) is a single-arm, open-label, multicenter, phase 2 study of ceritinib 750 mg/day (fasted) in adult patients with ALK+ (Vysis ALK Break Apart FISH Probe kit test), stage IIIB/IV NSCLC previously treated with alectinib and had subsequent disease progression. Other key inclusion criteria are ≥ 1 measurable lesion per RECIST 1.1 and WHO PS 0-1. Patients must have received previous treatment with alectinib, but prior crizotinib and/or up to 1 chemotherapy regimen are allowed. Patients with asymptomatic CNS metastases are eligible. Ceritinib may be continued beyond RECIST-defined PD. Primary endpoint is investigator assessed-overall response rate (ORR) per RECIST 1.1. Secondary endpoints include disease control rate (DCR), time to response (TTR), duration of response (DOR), PFS and safety. Biomarkers are evaluated for exploratory purpose.
Result:
Twenty patients were enrolled at 10 centers in Japan from Aug 2015 to Feb 2017. At present, the study is underway, and the results including ORR, DCR, TTR, DOR, PFS, safety and exploratory biomarker data will be presented at the 2017 WCLC.
Conclusion:
Section not applicable.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-021 - Efficacy of Single-Agent Chemotherapy after Exposure to Nivolumab in Advanced Non-Small Cell Lung Cancer (ID 8524)
09:00 - 16:00 | Author(s): Y.H. Kim
- Abstract
Background:
Recently, some retrospective studies suggested improvement of clinical outcome of patients with non-small cell lung cancer (NSCLC) receiving chemotherapy after immune checkpoint inhibitor.
Method:
We performed a single-center, retrospective study to compare overall response rate (ORR) and progression-free survival (PFS) in NSCLC patients who received single-agent cytotoxic chemotherapy after nivolumab (Group A) with those in NSCLC patients who received single-agent cytotoxic chemotherapy as 3[rd]-line or 4[th]-ine treatment without preceding nivolumab treatment (Group B). Patients with EGFR mutation or ALK rearrangement were excluded from this study.
Result:
Fourteen and 61 patients were were included in Group A and Group B, respectively. There were no significant difference of clinical characteristics between the two groups in terms of age, sex, smoking history, performance status and histology. Nab-paclitaxel was most frequently used in group A, while docetaxel was most commonly used in group B. Docetaxel or gemcitabine was significantly highly used in group B (7.1% vs. 54.1%, p < 0.01). The median administered line of nivolumab in Group A was 4. ORR was higher in Group A, but not significantly (14.3% vs. 8.1%, p = 0.610). Median PFS was compatible between the two groups (median, 56 days vs. 63 days, p = 0.425).
Conclusion:
Nivolumab might improve the efficacy of subsequent chemotherapy.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 3
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-013 - Efficacy and Safety of Nivolumab in Non-Small Cell Lung Cancer with Preexisting Interstitial Lung Disease (ID 8210)
09:30 - 16:00 | Author(s): Y.H. Kim
- Abstract
Background:
Patients with interstitial lung disease (ILD) have a higher incidence of non-small cell lung cancer (NSCLC) and have few treatment options for NSCLC. While immune checkpoint inhibitors (ICI) are used for NSCLC treatment, the incidence of ICI-related ILD in patients with preexisting ILD is still unknown. Therefore, we retrospectively evaluated the efficacy and safety of nivolumab in patients with NSCLC with preexisting ILD.
Method:
We reviewed patients who were administered nivolumab at National Hospital Organization Kyoto Medical Center, Kyoto University Hospital, and Japan Red Cross Fukui Hospital. All patients were initiated on nivolumab therapy between December 24, 2015 and December 31, 2016 and were reviewed until May 31, 2017 or the date of death. We compared the response rate (RR), disease control rate (DCR), overall survival time (OS), incidence of nivolumab-related ILD, and severity of nivolumab-related ILD between patients with and without preexisting ILD.
Result:
Of 173 NSCLC patients administered nivolumab, 14 (8%) had preexisting ILD. The major radiographic pattern of preexisting ILD was a non-specific interstitial pneumonia pattern (10 patients), followed by the usual interstitial pneumonia pattern (4 patients). The RR and DCR were 21% and 57% versus 12% and 40% in patients with and without preexisting ILD (p = .393 and p = .263), respectively. The median OS from the initiation of nivolumab was not reached (95% confidence interval [CI], 4.1 months to not analyzed [NA]) with preexisting ILD and was 11.7 months (95% CI, 7.5 months to NA) without ILD (hazard ratio, 0.71; 95% CI, 0.29 to 1.77). The incidence of nivolumab-related ILD was significantly higher with preexisting ILD than without ILD (50% vs 15%, p = .004); however, the incidence of grade 3 or 4 nivolumab-related ILD was not significantly different in those with and without preexisting ILD (14% versus 6.3%, p = .251). The median time to the onset of nivolumab-related ILD was 2.3 months (range, 0.5 to 4.0 months) with preexisting ILD versus 2.4 months (range, 0.03 to 12.4 months) without ILD. No ILD-related death occurred.
Conclusion:
Treatment with nivolumab in NSCLC patients with preexisting ILD might offer comparable efficacy to that in those without ILD. Although a higher incidence of nivolumab-related ILD was observed in patients with preexisting ILD, incidence of severe nivolumab-related ILD was not significantly different between those with and without preexisting ILD. Additional studies should be conducted to determine the efficacy and safety of nivolumab in patients with NSCLC with preexisting ILD.
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P2.07-017 - Association between Thyroid Dysfunction and Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Received Nivolumab (ID 8330)
09:30 - 16:00 | Author(s): Y.H. Kim
- Abstract
Background:
Nivolumab is one of immune-checkpoint inhibitors and has the first agent approved by the U.S. Food and Drug Administration for advanced non-small cell lung cancer (NSCLC). However, the rate of objective responses remains at approximately 20%.Additionally, immune-checkpoint inhibitors often have developed immune-related adverse events. We have previously reported that PD-L1 single nucleotide polymorphisms (SNPs) were possible biomarker for efficacy of nivolumab. We investigated the association between genetic polymorphisms in the PD-1/PD-L1 gene and clinical outcome for nivolumab including response and adverse events.
Method:
A total of 68 consecutive patients with NSCLC were treated with nivolumab from December 2015 to October 2016 at Kyoto University. Of these patients, 59 participated in the present study. The remaining 9 patients were excluded from this study because 3 patients declined informed consent, 2 patients had no follow up blood examination, one patient had a history of double cancer and 4 patients had determined as progression disease within 15days from the first administration of nivolumab. Seven SNPs (PD-L1; rs822339, rs1411262, rs2890658, rs4143815, rs2282055, PD-1; rs2227981, rs2227982) were genotyped using TaqMan genotyping assay. Response was assessed as per the Response Evaluation Criteria in Solid Tumors (version 1.1) by investigators respectively. Adverse events were assessed as per the Common Terminology Criteria for Adverse Events (version 4.0) by an investigator. We defined hyperthyroidism as elevated FT4 or FT3 and hypothyroidism as low FT4.We explored the association of adverse events and the PD-1/PD-L1 SNPs subtypes using the Cochrane-Armitage test and Fisher’s exact test as appropriate. Difference of progression free survival (PFS) between each group was assessed using the log-rank test.
Result:
Median PFS in this group was 67days (95% confidence interval, 54 to 107 days). Median PFS was significantly longer in patients with thyroid dysfunction than in those without thyroid dysfunction (152 vs 58 days; P = 0.0349). GG and GT genotype of rs2282055 were related to better PFS (82 vs 65 days; P = 0.0311). There were no significant association between thyroid dysfunction and SNPs. However, absence of thyroid dysfunction in patients with TT genotype of rs22282055 suggests that rs2282055 might be related thyroid dysfunction (P=0.1863 Fisher’s exact test).
Conclusion:
In the patients treated with nivolumab, GG and GT genotype of rs2282055 might be a predictive biomarker for response and might contribute the occurrence of thyroid dysfunction.
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P2.07-024 - Real-World Data of Nivolumab for Previously Treated Non-Small Cell Lung Cancer Patients in Japan: A Multicenter Retrospective Cohort Study (ID 8699)
09:30 - 16:00 | Author(s): Y.H. Kim
- Abstract
Background:
Real-world data in non-small cell lung cancer (NSCLC) patients treated with nivolumab are currently lacking. This study aimed to obtain a detailed understanding of the characteristics and outcomes of these patients.
Method:
We retrospectively analyzed data for stage IIIB-IV (7th edition) NSCLC patients treated with nivolumab between January 2016 and January 2017.
Result:
A total of 394 patients were included in the study. Most patients had a PS of 0 or 1 (76%) and non-squamous histology (80%). Epidermal growth factor receptor (EGFR) gene mutations were detected in 16% of all patients. Two hundred and seventy-two patients (69%) had received ≥ 2 prior systemic therapies. Response rate was 20.8 %, and median progression-free survival (PFS) was 2.2 months. Estimated PFS and overall survival (OS) at 1-year were 17 % and 55 %, respectively. Multivariate analysis using Cox proportional hazards models identified poor performance status (PS 2-4) and EGFR mutation as independent predictors of PFS (hazard ratio [HR] 2.17; 95% confidence interval [CI], 1.68 to 2.80, P<0.001; HR 1.44; 95% CI, 1.02 to 2.02, P=0.04, respectively). In 255 patients without these negative predictive factors for PFS, response rate was 27.3 %. In these patients, estimated PFS and OS at 1 year were 23 % and 64 %. Severe immune related adverse events (≥Grade 3) were identified in 11.2 % of all patients, and 8.3 % of the patients developed pneumonitis (any grade). Overall incidence of pseudoprogression was approximately 2 %.
Conclusion:
Nivolumab has demonstrated a favorable efficacy and safety profile in real-world patients. Poor PS and EGFR mutation positivity were independent negative predictive factors for PFS. Importantly, pseudoprogression was rare in real-world patients.
