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Kunihiko Kobayashi
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MS 14 - QOL Evaluation in Practice from the Viewpoint of Physicians and Nurses (ID 536)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Nursing/Palliative Care/Ethics
- Presentations: 1
- Moderators:Qing Zhou, Beth Eaby-Sandy
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 315
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MS 14.03 - Estimating Prognosis - How Accurate Can We Be? (ID 7708)
11:30 - 11:45 | Presenting Author(s): Kunihiko Kobayashi
- Abstract
- Presentation
Abstract:
In the lung cancer field, several studies have described the relationship between prognosis and quality of life (QoL), with most reports (Table 1), concluding a QoL evaluation of patients with advanced lung cancer before the start of chemotherapy could predict a patient’s prognosis. Such reports described common features: a poor prognosis for investigated patients whose disease was at an advanced stage and/or who were elderly, and the use of cytotoxic agents or irradiation, with poor efficacy. Molecular targeted drugs for epidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) fusion gene have recently been used in clinical practice. Such agents have led to dramatic improvements in patients with driver mutations. Indeed, we witnessed a “Lazarus response” during the NEJ001 study [1], which investigated the efficacy of an EGFR–tyrosine kinase inhibitor (TKI), gefitinib, for advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations with a poor performance status (PS): The PS improvement rate was 79% (p<0.00005); in particular, 68% of 22 patients improved from ≥PS 3 at baseline to ≥PS 1. And median survival time of the EGFR-mutated patients was 17.8 months, while that of the patients without EGFR mutations was 3.5 months. Unfortunately, following the introduction of “precision medicine” for lung cancer, few reports have described the relationship between prognosis and QoL. Herein, we describe NSCLC patients with an EGFR mutation treated with gefitinib or chemotherapy as first-line treatment in a randomized phase III study, termed NEJ002 [2]. The patients’ QoL was assessed prior to treatment and, thereafter, weekly by the Care Notebook [3]. The relationship between prognosis and QoL data, employed before and 4 weeks after the initiation of treatment, was analyzed by univariate and multivariate Cox regression. QoL data from 148 patients (72 in the gefitinib arm and 76 in the chemotherapy arm) were analyzed. Multivariate Cox regression showed that only a fatigue score on the Care Notebook assessed 4 weeks after the start of gefitinib could predict a patient’s prognosis. Other QoL scores, including those before starting not only gefitinib but also chemotherapy, did not affect survival. Estimating Prognosis - How Accurate Can We Be as the QoL Researcher? We hypothesize answers fall into two patterns: In the case of employing agents with a poor efficacy, such as cytotoxic agents, the QoL score before treatment should be evaluated as done previously. However, when treating with a very effective agent, the QoL score under treatment should be employed because any improvement in prognosis and QoL is strongly dependent on the efficacy of the agent. The next theme is “Estimating Prognosis of the Patient - How Accurate Can We Be as the Attending Physician? Unfortunately, we do not have rigid evidence for employing QoL assessments. Measuring QoL can have clinical benefits as well as research benefits. These include fostering patient–provider communication, helping clinicians and patients to identify problems and set priorities, and to assess therapy, palliative care, and rehabilitation. However, in my experience of validating the Japanese version of the EORTC QLQ-C30 [4], the answering rate for PS 0–2 patients was over 99% (225/228), but the corresponding rates for PS 3 and PS 4 patients were 81% (38/47) and 13% (9/69), respectively. Furthermore, multiple regression analyses showed that Symptom scale (coefficient: 0.188, p=0.001) and Emotional functioning (coefficient: 0.156, p=0.004) significantly related to Global QoL functioning in patients with PS 0-2; however, Symptom scale alone (coefficient: 0.220, p=0.042) significantly correlated to it in those with PS 3-4. Thus, when the patient concentrates on his/her symptoms and/or fails to respond a QoL questionnaire due to poor PS, a known adverse prognostic factor in advanced cancers, the attending doctor could recognize the patient’s short survival. Two studies have succeeded in showing the prolongation of patients’ survival under palliative care. Jennifer et al. [5] randomly assigned patients with newly diagnosed metastatic NSCLC to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. The FACT-L scale, including the lung cancer subscale (LCS) and Trial Outcome Index (TOI), measured at 12 weeks revealed that patients assigned to early palliative care had a better QoL than did patients assigned to standard care (p = 0.03). In addition, median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, p = 0.02). Basch et al. highlightened the importance of monitoring symptoms at ASCO 2017 [6]. Patients receiving routine outpatient chemotherapy for metastatic solid tumors, including lung cancer, were randomly assigned to self-report 12 common symptoms via tablet computers (“PRO intervention”), or to usual care. Median overall survival in the PRO intervention arm was 5 months longer than the control arm (31.2 vs. 26.0 months, HR, 0.832, p = 0.03). These two studies indicate that symptomatic QoL monitoring is critical for clinical practice and for predicting prognosis. Table 1 Studies on relationship between baseline QoL score and survival in advanced NSCLC patients
[1] Inoue A, et al. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol. 2009;27(9):1394-400. [2] Maemondo M, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-8. [3] Kobayashi K, et al. Validation of the care notebook for measuring physical, mental and life well-being of patients with cancer. Qual Life Res. 2005;14(4):1035-43. [4] Kobayashi, K, et al. A cross-validation of the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer Eur J Cancer 1998;34:810-815. [5] Temel JS, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-42. [6] Basch EM, et al. Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. (Abstract LBA2) presented in ASCO2017.Reference Therapy type Number of patients Questionnaire Prognostic, baseline scale/item Herndon et al. Cancer 1999, 85:333-340. Cisplatin/vinblastine 206 EORTC QLQ-C30 Pain Langendijk et al. Radiother Oncol 2000,55:19-25. External irradiation (>/=60 Gy) 198 EORTC QLQ-C30 Global QOL Moinpour et al. Qual Life Res 2002,11:115-26. Cisplatin+vinorelbine or Carboplatin+paclitaxel. 222 FACT-L Total FACT-L score Eton et al. J Clin Oncol 2003, 21:1536-1543. Cisplatin+etoposide or Cisplatin+paclitaxel 573 FACT-L + TOI Physical well-being and TOI Maione et al. J Clin Oncol 2005, 23:6865-6872. Vinorelbine+gemcitabine, Vinorelbine alone, or Gemcitabine alone 566 EORTC QOL-C30 Global QOL Sundstrøm S, et al, J Thorac Oncol. 2006;1(8):816-24. Palliative radiotherapy 301 EORTC QOL-C30 Appetite loss Efficace et al. Ann Oncol 2006, 17:1698-1704. Paclitaxel+cisplatin Gemcitabine+cisplatin Paclitaxel+gemcitabine 391 EORTC QLQ-C30 + QLQ-LC13 Pain, and dysphagia
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-010 - Updated Survival Outcomes of NEJ005/TCOG0902, a Randomized PII of Gefitinib and Chemotherapy in EGFR-Mutant NSCLC (ID 7948)
09:30 - 09:30 | Author(s): Kunihiko Kobayashi
- Abstract
Background:
North East Japan Study Group (NEJ) 005/ Tokyo Cooperative Oncology Group (TCOG) 0902 study has demonstrated that first-line concurrent (C) and sequential alternating (S) combination therapies of EGFR tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant NSCLC (ASCO2014, Ann Oncol 2015). However, overall survival (OS) data were insufficient because of the lack of death events in the primary report.
Method:
Progression-free survival (PFS) and OS were re-evaluated at the final data cutoff point (March 2017) for the entire population (N = 80).
Result:
At the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the C regimen and 15.3 months for the S regimen (p = 0.13). Median OS time was 41.9 with the C regimen and 30.7 months with the S regimen (p = 0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; p = 0.34). Patients who had common mutations showed no significant differences in PFS according to type of mutation. Patients with Del19 displayed relatively better OS (median: 45.3 and 33.3 months for C and S regimens) than those with L858R (31.4 and 28.9 months). No severe adverse events including interstitial lung disease have occurred during the follow-up period since the primary report. In an exploratory analysis, there was no significant difference in post progression survival and overall survival between patients with progression of target or non-target lesions and those progressed with new lesions.
Conclusion:
This updated analysis has confirmed that PFS is improved with first-line combination therapies compared to that with gefitinib monotherapy, and the C regimen in particular offers an overall survival benefit of 42 months in the EGFR-mutated setting. Our on-going NEJ009 study will clarify whether this combinational strategy can be incorporated into routine clinical practice.
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P2.03-021 - A Phase I Study Evaluating the Combination of Afatinib, Carboplatin and Pemetrexed after Failure of 1<Sup>St</Sup> Generation EGFR-TKIs (ID 8713)
09:30 - 09:30 | Author(s): Kunihiko Kobayashi
- Abstract
Background:
Despite the high response rate in patients with EGFR-mutation positive NSCLC, treatment with EGFR-TKIs is not curative and eventually there is disease progression. In patients with acquired resistance to 1[st] generation EGFR-TKIs, previous studies have demonstrated that afatinib had some clinical activity. We previously reported that the combination of gefitinib, pemetrexed and carboplatin showed promising antitumor efficacies in EGFR-mutated lung cancer patients. In this phase I trial, we assessed the safety and efficacy of afatinib combined with pemetrexed and carboplatin in NSCLC patients who acquired resistance.
Method:
Patients with EGFR-mutation positive metastatic NSCLC, who had received 1[st] line gefitinib or erlotinib and developed disease progression were eligible. Patients received pemetrexed 500 mg/m[2] and carboplatin AUC=5 on day 1 in all cohorts, and afatinib at doses of 20, 30 and 40 mg/body from day 8 to 18 of 21-day cycle. DLT was assessed after the first cycle, and doses were escalated in cohorts of 3 to 6 patients.
Result:
Eleven patients were enrolled to this trial and 9 patients were evaluable for safety and efficacy. At an afatinib dose of 30mg/body, 3 patients experienced DLT (grade 3 diarrhea, grade 3 hypokalemia, grade 4 thrombocytopenia, grade 3 amylase elevation and grade 3 gamma-glutamyl transferase). The overall response rate was 20% (95% C.I. 5.7 to 51) and median progression free survival was 16.2 months (95% C.I. 4.7 to not reached).
Conclusion:
The MTD of afatinib is 20mg/body in combination with pemetrexed 500 mg/m[2] and carboplatin AUC=5 on day 1 every 21 days. This combination demonstrated activity in EGFR mutation positive NSCLC with acquired resistance to 1[st] line EGFR-TKIs.
