|Year : 2017 | Volume
| Issue : 1 | Page : 182-186
First-line therapy outcomes in patients with advanced stage nonsmall cell lung cancer treated at nongovernment tertiary care centrer in India: Experience from a real world practice
SS Hingmire, MB Sambhus, DS Kelkar, SW Joshi, KS Narsinghpura
Department of Medical Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
|Date of Web Publication||1-Dec-2017|
Dr. S S Hingmire
Department of Medical Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Reports on first line or subsequent treatment and their outcomes for patients with advanced nonsmall cell lung cancer (NSCLC) in India are scarce. The present study is an attempt to understand real world practice scenario of first-line therapy and outcome in advanced stage NSCLC patients. METHODS: Observational study was conducted at a nongovernment tertiary cancer care center. Totally 83 patients with newly diagnosed advanced NSCLC who were evaluated for further treatment from 2008 onward were included in the study. RESULTS: Best supportive care was the only treatment received in 11/83 patients. Sixty-three patients received platinum-based doublet chemotherapy and nine received epidermal growth factor receptor tyrosine kinase inhibitor (TKI) as first-line therapy. Pemetrexed and platinum was the most common first-line chemotherapy (56%) regimen used. First-line chemotherapy had to be discontinued in these eight patients due to Grade III/IV toxicity. Disease control rate with the first-line chemotherapy was 70% (partial response 38%, stable disease 32%). Median overall survival (OS) was 17 months with OS at 1 and 2 years was 52% and 29.5%, respectively. CONCLUSION: First-line platinum-based chemotherapy is feasible and does achieve disease control in the majority of patients with advanced NSCLC. Strategies of selection of therapy based on histology and the presence of driver mutations, use of small molecule TKI, maintenance therapy and multiple lines of therapies are being increasingly implemented in clinical practice and thus improving survival of Indian patients of NSCLC.
Keywords: Advanced nonsmall cell lung cancer, first line therapy, Indian patients
|How to cite this article:|
Hingmire S S, Sambhus M B, Kelkar D S, Joshi S W, Narsinghpura K S. First-line therapy outcomes in patients with advanced stage nonsmall cell lung cancer treated at nongovernment tertiary care centrer in India: Experience from a real world practice. Indian J Cancer 2017;54:182-6
|How to cite this URL:|
Hingmire S S, Sambhus M B, Kelkar D S, Joshi S W, Narsinghpura K S. First-line therapy outcomes in patients with advanced stage nonsmall cell lung cancer treated at nongovernment tertiary care centrer in India: Experience from a real world practice. Indian J Cancer [serial online] 2017 [cited 2019 Oct 18];54:182-6. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/182/219594
| » Introduction|| |
Lung cancer is the leading cause of cancer death globally. Patients with advanced stage nonsmall cell lung cancer (NSCLC) have improved survival and quality of life with platinum-based double chemotherapy. Further strategies of the second line and subsequent chemotherapy, maintenance chemotherapy have added to the survival and better pallation in these advanced stage NSCLC patients. Identification of driver mutations in genes like epidermal growth factor receptor (EGFR), ALK and availability molecularly targeting agents like tyrosine kinase inhibitors (TKIs) have made the greatest impact in the management of advanced NSCLC and has improved survival beyond 2 years in a subgroup of patients with metastatic NSCLC.
Medical oncologists in India do have access to the various advances in the diagnostics and treatment modalities in cancer management including NSCLC. However, resource constraints may limit practical application of these in daily patient management. The present study is an attempt to understand real world practice scenario of epidemiology, therapeutic trends, and outcome in advanced stage NSCLC patients treated at a nongovernment tertiary care center in India.
| » Methods|| |
This observational study was conducted at a nongovernment tertiary cancer care center in India. Eight-three patients with newly diagnosed advanced stage NSCLC who were evaluated for further treatment from 2008 onwards till date were included in the study. Baseline characters related to demographic data, clinical presentation, and diagnosis, treatment delivered and outcome of these patients were evaluated with the help of predefined proforma.
Ten patients out of the 83 received palliative best supportive care (BSC) alone without any specific cancer therapy and these were excluded from the analysis of treatment-related outcomes.
Patients who received at least two cycles of chemotherapy or 6 weeks of oral TKIs as first-line therapy were included in the first line therapy response analysis.
Response rates post first-line therapy was estimated after response evaluation according to RECIST criteria.
Statistical analyses were carried out using the SPSS software version 15.0. Overall survival (OS) analysis was performed by Kaplan- Meier product limit method. OS was measured from the date of diagnosis to the date of death or the last date of follow-up. Univariate analyses were performed for various independent prognostic factors for survival by Cox regression analysis.
Seventy-three patients were eligible for OS analysis.
| » Results|| |
The main baseline clinical characteristics of the patients are shown in [Table 1]. Median age was 62 years (30–82 years), of which 64% were men. Fifty-six percent of patients had Eastern Cooperative Oncology Group performance status (PS) of 2 at diagnosis, whereas 42% were in PS 1. Various comorbid conditions were noted in 36 out of 83 patients. Twenty-one percent of the patients were past or current smokers.
Diagnosis of NSCLC was based on histopatholgical examination of biopsy tissue obtained from primary or metastatic sites in 84% of patients, however, in remaining, only cytology was available for diagnosis.
Adenocarcinoma was the most common histopathological subtype seen in 74% of patients, 14% had squamous cell variety. EGFR mutation analysis was performed in 38 out of 83 patients and was positive in 34% of these. Only one patient tested positive for ALK mutation.
Pleural effusion was present in 35% patients at diagnosis. Various sites of metastasis were opposite lung (23%), bones (17%), liver (13%), and adrenals (3%). Ten patients had brain metastasis at diagnosis.
Antituberculosis treatment was received by ten patients the presenting symptoms before the final diagnosis of lung cancer was confirmed.
BSC was the only treatment received in 11 out of 83 patients. Sixty-three patients received platinum-based doubletchemotherapy and nine received oral EGFR TKI as first line therapy. Pemetrexed and platinum was the most common first line chemotherapy (56%) regimen used. Taxane and platinum combination was administered as first-line chemotherapy in 23 patients. Seven patients defaulted for continuation of chemotherapy after the first cycle for financial/social reasons. One patient developed Grade III toxicity (neuropathy) after first cycle of paclitaxel-carboplatin chemotherapy. One patient died due to unrelated cause-hypertensive bleed. These 9 patients who received only one cycle of first-line chemotherapy were not included for first line therapy outcome analysis.
Six patients out of nine who received EGFR TKI as first-line therapy had EGFR mutations. In remaining three patients, EGFR mutation status was unknown.
Pemetraxed continuation maintenance was administered in 5 patients, and 12 patients received switch maintenance with oral EGFR TKI. Second and third line therapy was received in 33% of patients while 7% were eligible for third line therapy.
Efficacy, survival, and toxicity
Thirty-eight percent patients had partial response (PR) with first line chemotherapy, and 32% of patients had stable disease (SD). Thus, disease control rate (DCR) with the first line chemotherapy was 70%. Out of nine patients who received oral EGFR TKI as first-line therapy, seven patients achieved PR, and one had SD.
Median OS was 17 months with OS at the end of 1 and 2 years was 52% and 29.5%, respectively [Figure 1]. On univariate Cox regression analysis no statistically significant difference was noted in OS with respect to age, sex, PS score, histopathological subtypes or EGFR mutation status. Better OS was observed in females (P - 0.064) [Figure 2] and patients with EGFR mutations (P - 0.194) [Figure 3].
|Figure 3: Overall survival in patients with epidermal growth factor receptor positive versus epidermal growth factor receptor negative|
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Grade III neuropathy was observed in two patients receiving paclitaxel platinum chemotherapy. Five patients receiving first-line chemotherapy experienced Grade III/IV bone marrow suppression and one patient developed infusion reaction with pemetrexed. Thus, first line chemotherapy had to be discontinued in these eight patients due to Grade III/IV toxicity. [Table 2].
| » Discussion|| |
Baseline characteristics such as age, male to female ratio, histopathological subtypes, sites of metastasis and EGFR mutation positivity rates as noted in our study population are in concordance with those reported in prior epidemiological studies from India.,
Reports on the first line or subsequent treatment and their outcomes for patients with advanced NSCLC in India are scarce. Multiple factors influence decision for selection of first-line therapy in advanced stage NSCLC., Most important ones would be age, comorbid conditions, PS at diagnosis, histopathological subtype adenocarcinoma versus nonadenocarcinoma, and since past few years presence or absence of driver mutations in genes such as EGFR and ALK. Resource limitations, social factors are also important considerations.
Ten patients did not receive any specific cancer therapy and were offered only BSC as palliation. Poor PS, advanced age, significant comorbid medical conditions, and extensive tumor burden were the reasons for selection of BSC as the only treatment offered. Davidoff et al. reported age, health status and tumor characteristics as the determinants of receipt of chemotherapy in patients with advanced stage NSCLC. Only 25.8% of 21,285 patients with advanced stage NSCLC above the age of 66 years incident from 1997 to 2002 received first-line chemotherapy. In a study reported from South India, 6.2% of patients were deemed unfit and referred for BSC.
However, recently the availability of the molecularly targeting agents like EGFR TKI with better efficacy and excellent tolerability has been associated with “Lazarous responses” in select subgroup of elderly or poor PS advanced stage NSCLC patients with presence of driver mutations. Thus today histopathological subtypes and presence or absence of driver gene mutations are more significant determinants of receipt of systemic therapy in NSCLC than age or PS.
Nearly 76% of the patients in our study received chemotherapy, and 11% received oral EGFR TKI as first line therapy. Platinum-based doublet chemotherapy was used as standard regimen for all patients. Pemetrexed was the most common combination drug selected for patients with adenocarcinoma subtype while taxanes were chosen for squamous histology. This reflects concordance with the established, global NSCLC management guidelines and practices.
Six out of the nine patients who received EGFR TKI as first-line therapy tested positive for EGFR mutations. In remaining three patients EGFR mutation status was unknown, however, these patients refused chemotherapy, and EGFR TKI was chosen as first line therapy on the basis of older clinical criteria for benefit from EGFR TKI viz., adenocarcinoma, nonsmokers, and females. In the study reported by Noronha et al. of 111 patients selected for EGFR TKI therapy based on clinical criteria, 92 patients received EGFR TKI as first line therapy. Retrospectively 39/111 patients tested positive for EGFR mutations. In another study from India, 39.2% of patients received first-line gefitinib and 60.8% of patients received first-line chemotherapy. Bhatt et al. reported the use of upfront TKI in 14.15% of patients.
With the established role as predictive marker for EGFR TKI, EGFR testing is being increasingly incorporated in practice before selection of first-line therapy. However, need for biopsy for adequate tissue, time taken for availability of the report, availability of test facility and cost may limit uniform application of this approach.
Pemetrexed maintenance and EGFR TKI maintenance therapy was received by 6.8% and 16.4% of patients, respectively, as compared to 14.15% and 24.52% as reported by Bhatt et al.
In spite of established benefit of pematrexed maintenance and recommendations from global management guidelines utility of the same in clinical practice in India may be limited in view of various factors like need for continued hospital visits, intravenous mode of administration and the cost.
DCR of 70% was noted in our study with PR in 38% and SD in 32% of patients with first-line chemotherapy. Bhatt et al. reported overall response rates of 67. 6% with first line chemotherapy.
However, in 12% of patients first line chemotherapy had to discontinue before completion of planned number of cycles due to various Grade III/IV toxicities.
Median OS of the entire unselected study population was 17 months with 1 and 2 year OS rates of 52% and 29.5%, respectively. Survival of patients with advanced stage NSCLC as reported in other studies from India is shown in [Table 3].
The outcome of first line therapy is improved by strategies like use of pemetrexed for adenocarcinoma subtype,, identification of driver mutations and use of EGFR or ALK TKI in mutation positive patients. The addition of monoclonal antibodies like bevacizumab and cetuximab to platinum-based doublet chemotherapy in the first line has been reported to improve survival in patients with advanced NSCLC.,
Median OS as reported from various trials and meta-analysis for patients with driver mutations and those without are 22 months and 13–17 months, respectively.
Thus, the benefit of first-line chemotherapy in Indian patients is consistent with that reported from global clinical trials.
| » Conclusion|| |
This study shares the real world practice experience of treatment outcomes of patients of advanced NSCLC in India. First line platinum-based chemotherapy is feasible and does achieve disease control in the majority of patients with advanced NSCLC. Strategies of selection of therapy based on histology and presence or absence of EGFR and ALK mutations, use of small molecule TKI, maintenance therapy and multiple lines of therapies are being increasingly implementred in clinical practice and thus improving survival of Indian patients of NSCLC.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]