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K. Prabhash



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    P1.09 - Poster Session 1 - Combined Modality (ID 212)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P1.09-006 - Chemo-Radiotherapy For Locally Advanced NSCLC In Resource Limited Population: Is It Isoeffective? (ID 836)

      09:30 - 09:30  |  Author(s): K. Prabhash

      • Abstract

      Background
      Annually 63,000 approximately new patients of lung cancer are diagnosed in India, with two-third of them in advanced stage at presentation.. Radiotherapy with concurrent chemotherapy has shown survival benefit and is the standard of care for this group of patients in western literature.

      Methods
      One hundred seventy four consecutive patients Of Non Small cell Lung cancer (NSCLC) were treated with radical (chemo)-radiotherapy at Tata Memorial hospital from January 2008 to December 2012, . Detailed study of patient, tumour and treatment related factors were performed. Outcomes in the form of progression free survival (PFS) and overall survival (OS) at two years were calculated. Follow-up and analysis of data was performed in February 2013. Univariate and multivariate analysis was performed to see the impact of patient related factors like age, smoking, KPS, presence of comorbidity, tumour related factors including T stage, N stage and stage group and treatment related factors chemotherapy timing , total dose, duration of radiotherapy and response to treatment on PFS and OS.

      Results
      Of 174 patients, Males were 154(88.5%) with median age of 58 years (range 30-84 years) and 121(69.5%) were smokers. Median KPS was 80 (range 60-100) and 59 patients had significant comorbidity. Cough was the commonest presenting symptom (28%) followed by chest pain (27%) and haemoptysis (24.7%). Most common histology was squamous carcinoma 47.1% followed by adenocarcinoma in 41.4%. Stage III (A+B) constituted 90.2% of the patients. All patients received thoracic radiotherapy using 3D Conformal technique using 6/15 MV photons to a median dose of 60Gy (range 4-66Gy) over a median duration of 44 days(2-85 days) .Of 174 patients 166 patients (95.4%) completed the planned treatment. Median GTV and PTV volumes were 132 cc (16.7-741cc) and 538 cc(56-5680 cc) respectively. The median lung-PTV volume was 2599cc and V20 Gy was 23.79 %. Out of 174 patients 76% patients received concurrent chemotherapy, while 11.5% received sequential chemotherapy also. Response assessment using WHO criteria was done at 2 months post treatment, 63 (36.1%) had complete response whereas 64patients (36.8%) had partial response or stable disease and 7 patients(3.4%) had progressive disease . At last follow-up of with mean follow up 9.3 months (range 0-37 months), 32 patients had loco-regional recurrence and 33 patients had distant metastases. Acute pneumonitis grade I and II was observed in 87(50%) and 13(7.4%), acute oesophagitis grade II and III was seen in 56(32.1%) and 7(4%) patients respectively as per RTOG grading. Median PFS and OS were 20 months and 23 months with the estimated 2 year PFS & OS was 35% & 47.4%respectvely.On Univariate analysis, complete response to treatment (p=0.000) had favourable impact on PFS whereas smoking (p=0.009), advanced T stage (p=0.002) and less than complete response (p=0.000) had negative impact on OS.

      Conclusion
      Even under resource limited conditions patients who were treated with an intensive (chemo) radiation with supportive care had an acceptable treatment compliance and comparable treatment outcomes. , Patients with advanced stage and smokers did worse. Patients treated with concurrent chemoradiation and complete responders had better OS.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-030 - Comparative Pharmacokinetics of Two Formulations of Pemetrexed in Indian Adult Chemo-Naive, Adenocarcinoma Non-Small Cell Lung Cancer Patients. (ID 1565)

      09:30 - 09:30  |  Author(s): K. Prabhash

      • Abstract

      Background
      Pemetrexed (Alimta, Eli Lilly) with platinum doublet is an effective drug for first-line treatment of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC). Innovator products are generally highly priced which limits their utility in developing countries. In India, a generic formulation (Pemgem, Dr. Reddy’s Laboratories) is marketed at 25% the cost of Alimta. Results of a study comparing the pharmacokinetic and safety profile of the two formulations of pemetrexed are discussed here.

      Methods
      This study was approved by TMC-ACTREC-IRB and registered with Clinical Trials Registry- India (CTRI). Patients were enrolled from a tertiary care cancer hospital in India as per predefined selection criteria mentioned the protocol. Pemetrexed (500 mg/m[2]) was administered as a 10 minute short infusion. All patients received standard premedication. Pharmacokinetic blood samples were collected at predose and 10 minutes (just before end of infusion), 15 min., 30 min., 50 min., 1 hr., 1 hr. 20 min., 2 hrs.,4 hrs.,6 hrs., 8 hrs. and 24 hrs after starting the infusion. Plasma pemetrexed levels were determined by a validated HPLC method. Toxicity was graded using CTCAE v. 4.03. Quality of life questionnaire was taken at baseline and at end of 3rd cycle.

      Results
      Twenty four patients were enrolled on the study, eight in Alimta arm and sixteen in Pemgem arm. Patient demographics were comparable in the two arms. Mean Area Under the Concentration-Time Curve (AUC~0-24 hr~) was 222.06 vs. 253.7 mg h/L and mean C~max ~was 106.5 and 130.7 mg/L in Pemgem and Alimta arms respectively. Volume of distribution of pemetrexed was 16.59 and 17.56 L, clearance was 3.83 vs. 4.3 L/hr and half-life was 3.29 and 2.43 hr in the two arms respectively. Toxicity was comparable between the groups. However, a higher incidence of grade III/IV hyponatrimia (25%) was observed in our patients which needs to be investigated further. Global health status improved significantly in both treatment arms at the end of 3 cycles compared to baseline. Pooled data of selected Quality of Life indices is shown below. Table 1: Mean difference in selected Quality of Life indices (3rd Cycle Vs. Baseline)

      QOL scale Mean difference SEM P value
      Global health status 18.39 3.10 0.001
      Pain -7.77 3.46 0.023
      Dysponea -7.77 3.81 0.05
      Insomnia -4.44 3.06 0.017
      Haemoptysis -3.33 2.10 0.043

      Conclusion
      Pemgem had similar pharmacokinetic and safety profile as Alimta. Generic substitution would be cost effective and likely to yield comparable efficacy.

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    P1.24 - Poster Session 1 - Clinical Care (ID 146)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P1.24-037 - Addition of bevacizumab to standard palliative chemotherapy in advanced non squamous cell lung carcinoma: Tata Memorial Hospital experience. (ID 2743)

      09:30 - 09:30  |  Author(s): K. Prabhash

      • Abstract

      Background
      Outcome of advanced NSCLC is poor. Platinum based chemotherapy is standard of care. Addition of antiangiogenic agent such as bevacizumab improves the results.

      Methods
      Prospectively collected data of patients received bevacizumab, platin and pemetrexed as initial therapy for 6 cycle followed by maintenance pemetrexede and bevacizumab till disease progression or unacceptable toxicity.

      Results
      We had 18 patients, 14 were males and 4 were females. The age of the patients ranged from 45 to 68 years with a median age of 54 years. About one third of the patients were smokers and most of the patients were of good performance status (ECOG-0/1-94%). The most common symptoms of presentation were, cough in 61% of patients followed by dyspnea in 39% of patients. The chest pain and neck swelling were present in 11% of patients whereas bony pains were present in 39% of patients. Co-morbidities of diabetes and hypertension each were present in 17% of patients. Most of the patients were stage IV(94%). The patients received chemotherapy which comprised of pemetrexed, platin and bevacizumab for 6 cycle followed by pemetrexed and bevacizumab maintenance till progression in responding patients after six cycle. Number of cycle’s received ranged from 2 to 21 with a median of 10 cycles. Response rates achieved were stable disease in 72%, partial remission in 22% with disease stabilization rate of 95%. Grade 3 and 4 toxicities observed were neutropenia 11%,proteinuria 11%, anemia and Hyponatremia were present in 17%.One patient each developed pulmonary thromboembolism and hypertension. Bevacizumab was stopped because of toxicitty in one patint who developed pulmonary throboembolism. Median progression free survival was 7 month and median overall survival for whole group is not reached.

      Conclusion
      Addition of bevacizumab to standard platin based therapy in both initial and maintenance phase is feasible with acceptable toxicities. Some patients have long term disease control.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-056 - A Tertiary cancer experience in use of TKI in metastatic lung cancer (ID 3351)

      09:30 - 09:30  |  Author(s): K. Prabhash

      • Abstract

      Background
      Use of tyrosine kinase inhibitors is a attractive option due to its predicatble profile of side effects & it been a oral tablet. Its efficacy and toxicities have been well described in both east asian and western population. However not much literature is available on its use from India. The aim of this paper was to audit the population which received TKI (Erlotinib or Gefinib) in a tertiary cancer center in India.

      Methods
      All patients who received TKI in lung cancer were identified from our OPD database. There case records, electronic medical records & our OPD databases were utilized. The demographic profile, the staging details , details of EGFR mutations, the RECIST response rates, the toxicities, progression free survival (PFS) & overall survival (OS). SPSS 16 was used for statistical analysis.

      Results
      Total of 105 patients were identified with a median age of 58 years (35-77 years). There were 56 females (52.8%). The 15.2 % (16) of patients were smokers & 22.3 % (18) were tobacco chewers. The median duration of smoking & tobacco chewing was 25 & 15 years respectively. All patients had stage IV disease. There were 2 cases of squamous cell carcinoma (1.9%)& rest all were adenocarcinomas. (98.1%) Extrathoracic disease was present in 42 patients (39.6 %) The EGFR mutation invoved exon 19 , 21 & 18 in 25, 72 & 8 patients respectively. The ECOF PS was 0 & 1 in 14 (13.2%) & 51 (48.1%) patients respectively.The incidence of any grade skin and mucosal toxicites were 53% & 38% respectively. The median PFS & OS overall were 11.1 & 21 months respectively. The PFS & OS were not affected by the performnce status, comorbidities & sites of metastasis

      Conclusion
      Use of TKI in Indian population had similar toxicity & efficacy as reported in literature.

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    P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.02-018 - EGFR mutation and its subtypes in Indian population: a study from single academic centre- Tata Memorial Centre (ID 2965)

      09:30 - 09:30  |  Author(s): K. Prabhash

      • Abstract

      Background
      Tyrosine Kinase (TK) domains are central regulators of signaling pathways that control differentiation, transcription, cell cycle progression, apoptosis, motility and invasion. EGFR TK mutations represent bona fide somatic mutations in NSCLC. Patients with specific mutations respond better to targeted therapy.Mutation analysis is known to be evaluated by several methods. Real time PCR using allele specific TaqMan primer probes is a simple, robust, highly sensitive, and selective method that is compatible with standard processes used for known gene expression analysis. The main objective of our study was to detect EGFR mutations in NSCLC patients registered in Tata Memorial Hospital (TMH) by using rapid and sensitive technique of RQ-PCR with In-house TaqMan primer probes. There is limited data regarding EGFR mutation in Indian population with variable mutation rate reported. This is an attempt to get actual mutation rate in our population, correlate the frequency of EGFR mutation and their subtypes and analyze across different variables of age, gender, habits and histology with different ethnicity groups.

      Methods
      1018 patients of NSCLC were referred for EFGR testing as a routine service over a 1.5-year period. Extracted DNA from FFPE blocks was amplified for the exons 18, 19, 20 and 21 using the specific TaqMan primer probes with the End point genotyping method on LC-480 II platform. Chi-square test was performed to reveal any significant correlation between the mutation status and age, gender and habits of the patient and tumor histology.

      Results
      Overall Mutation Rate (MR) was 25.0% with a higher mutation rate in females than males (34 vs.21) with a p value of 0.002. Within the age group, MR was high in > 60 yrs group as compared to <60 years (47.6 % vs. 31%). Total population of smoker vs. never-smoker was 37.5% vs. 58.6 %. (p value <0.001). MR was significantly higher in Never Smoker (NS) as compared to Smoker (S) (31.5 % vs.16 %), MR in Adenocarcinoma (ADC) was significantly higher than squamous (27.7 %vs. 5.6%) with a p value of <0.001. MR is higher in ADC NS female as compared to ADC NS male (37.2 %vs.29 %). MR of Exon 19 , 21, 18, & 20 was 53%, 38 %, 5.8 % & 2.4 % respectively. In the cohort of ADC NS gender, Exon 19 positivity was predominantly higher in male than female (61.8% vs.34 %) , whereas Exon 21 was marginally higher in ADC NS female than male (39 % vs 34 %). Exon 20 expressed 2.4%.

      Conclusion
      There is a heterogenous EGFR MR in diferent geographical population. We are in close association with East Asian countries than Western countries. In our data though the MR is high in NS, 16 % of EGFR MR in smokers is also startling reality. Another possibility of variation in EGFR mutation rate could be due to application of different technologies. Each technique differs in their sensitivity and specifictiy. EGFR tyrosine kinase domain define a new molecular marker for lung carcinoma.