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A. Joshi
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-021 - FISH and IHC Discordance in ALK Rearranged Non Small Cell Lung Cancer (ID 10474)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
There is a small proportion of lung cancer patients who are ALK positive by IHC but negative by FISH, or vice versa. Outcome of this subset of patients when treated with crizotinib is not well known. This analysis was planned to study the FISH and IHC discordance in ALK rearranged NSCLC.
Method:
We retrospectively collected data from a prospectively maintained database in medical oncology department. We analyzed 257 patients who had been diagnosed with ALK rearranged NSCLC cancer. Patients who had discordant FISH and IHC findings for ALK were selected for this analysis. Their response rates, progression free survival and overall survival were calculated. Progression free survival and overall survival were estimated using Kaplan Meier method.
Result:
Out of 257 patients, 28 patients (10.9%) had discordance. 7 patients had IHC -ve status while had FISH positive status for ALK rearrangement. 21 patients had vice-versa. The response rate for crizotinib in IHC-/ FISH+ was 57.1% versus 71.4% in IHC+/FISH - group ( p-0.331). The overall median progression free survival was 8.7 months and median overall survival was not reached. There was no statistical difference in PFS and OS between the 2 groups.
Conclusion:
In around 1/10th of ALK rearranged NSCLC patients, FISH and IHC have discordant findings, however these patients also benefit from crizotinib.
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P1.01-023 - ALK-Positive NSCLC: A TMH Experience (ID 10491)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
ALK gene rearranged NSCLC are a rare subset of lung cancers. However, treatment with crizotinib leads to an improvement in outcomes. In this study, we have audited the outcomes of ALK-rearranged NSCLC at our institute.
Method:
This was a subset analysis of a prospective observational study. It was approved by the institutional ethics committee and was carried out in accordance with good clinical practice guidelines and declaration of Helsinki. For this analysis all Alk rearranged NSCLC patients, diagnosed at our center between November 2011- April 2017 were selected. The treatment received and the outcomes were noted. Progression-free survival and Overall survival were estimated using Kaplan-Meier method.
Result:
We had diagnosed 257 patients during this period. The median age was 50 years ( 23-77 years). There were 102 females (39.7%) and 155 males (60.3%). Only 49 patients were smokers (19.1%). The ECOG PS was 0-1 in 197 patients (76.7%), 2 in 28 patients (10.9%) and 3-4 in 32 patients (12.4%). The median number of sites of metastasis was 2 (0-7). Brain metastasis was seen in 36 patients (14.0%). The upfront treatment received was crizotinib in 168 patients (65.3%), pemetrexed -platinum doublet in 57 patients (22.2%), taxane-platinum in 4 patients (1.6%), gemcitabine-platinum in 4 patients (1.6%), others in 14 patients (5.4%). The crizotinib received was started upfront in 88 patients and after a few cycles chemotherapy in 80 patients. In these 80 patients, 53 patients were started as soon as the ALK rearrangement report was available while 27 patients were started after a few cycles once finances were available. The median PFS for crizotinib was 16.1 months versus 11.4 months in pemetrexed platinum (p-0.159) The median PFS in the patients receiving upfront crizotinib was 17.1 months versus 14.7 months in patients receiving crizotinib after the switch (p-0.399). The median overall OS was 39.9 months and it was similar between the two strategies of crizotinib(p-0.964). There were 57 patients (22.1%) who never received crizotinib. The median OS in patients who never received crizotinib was 11.0 months versus it was not reached in patients receiving crizotinib in any line (p-0.000). The 3 year OS in patients receiving crizotinib in any line was 67.0%.
Conclusion:
Crizotinib substantial improves outcomes in ALK-rearranged patients whether given upfront or post start of few cycles of chemotherapy.
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P1.01-024 - Plasma Circulating cfDNA as a Potential Biomarker in Clinical Management of NSCLC: Experience of Tata Memorial Hospital, India (ID 7975)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
Circulating cell free tumor DNA (ctDNA) from liquid biopsy is a potential source of tumor genetic material in absence of tissue biopsy for EGFR testing. NSCLC patients with detectable levels of oncogenic driver mutations in peripheral blood are known to be associated with more advanced disease and poorer prognosis. Liquid biopsy was performed on132 NSCLC patients with matched tumor tissue for genomic analysis. An EGFR mutation of one major molecular subtype in NSCLC was performed on massive parallel sequencing. The Study’s primary goals were to: (1) Derive high concordance between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the EGFR gene. (2) Establish and validate Liquid biopsy as a clinically useful surrogate for tissue biopsy in NSCLC whenever tissue biopsy is unavailable and (3) Treatment monitoring and detection of early recurrence.
Method:
Single gene EGFR mutation analysis was performed on the ctDNA by using ultra deep sequencing on the HiSeq platform. Then custom designed bioinformatics algorithms were used to detect somatic mutations at allele frequencies as low as 0.01%.
Result:
Overall concordance of mutation status between 132 pairs of tissue and plasma ctDNA samples for EGFR mutation status was about 97%. 34% (45/132) of the study subset was EGFR mutated on tissue typing and 31% (41/132) in ctDNA, with 100% specificity, 91.1% sensitivity. Positive predictive value was 100% and negative predictive value was 95.6% - with diagnostic accuracy of 97%. A false negative rate of 3% was observed in this study. 14 out of 132 (10%) samples which had rare Exon19 deletions and complex indels could be confidently detected by NGS methods. 6/31 patients (19%) who could not go for biopsy got the EGFR mutation testing on plasma alone, who were positive for Exon19/ Exon21 hotspot mutations could benefit from targeted therapy. An objective efficacy response rate for Gefitinib was estimated at 74%, with a disease control rate of 95.7%. Median period of follow-up was 13.9 months. Median PFS was 18.933 months (95% CI 11.168-26.198) and overall survival was 78.3%.
Conclusion:
10% of newly diagnosed NSCLC patients could get the additional benefit of targeted therapy, by using the NGS which detected recurrent novel HOTSPOT mutations. Liquid Biopsy based tests will soon be as widespread as “standard” biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information and would promisingly move from research into clinical practice in lung cancer.
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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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P1.03-021 - A Prospective Observational Study to Evaluate Incidence of Thromboembolic Events during Platinum Based Chemotherapy in Lung Cancer (ID 8131)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
Lung Cancer is a prothrombotic state with its treatment frequently complicated by thromboembolism leading to shorter life expectancy, worsening of the quality of life and may delay, interrupt, or completely halt the cancer therapy. Based on many retrospectives and prospective analyses in patients with lung cancer, thromboembolic complications are a common event with incidences ranging from 10-17 %. It is possible to identify those with the highest risk of venous thromboembolism suitable for antithrombotic prophylaxis, which could favorably affect their morbidity and mortality
Method:
All patients with advanced lung cancer who were started on platinum-based chemotherapy were included. Those patients who had prior TEs or inherited coagulopathy or those on therapeutic anticoagulation, regular NSAIDs / aspirin or those on bevacizumab were excluded.A thromboembolic event was considered associated with chemotherapy if it occurred between the time of the first dose and 4 weeks after the last dose
Result:
A total 188 patients were screened for the study and 167 patients were enrolled in the study. Since 2 patients were lost to follow-up after accrual, 165 patients were included in the final analysis. Of the 165 patients, 67.8% (112/165) received chemotherapy regimen of carboplatin with gemcitabine, 30.3% (50/167) received carboplatin with pemetrexed, 1.2 % (2/165) received cisplatin with pemetrexed and 0.6 % (1/165) received carboplatin with paclitaxel. A median number of days on platinum were 94 (range 10-478). The median number of chemotherapy cycles administered was 4 (range 1–6). Thromboembolic events occurred in 4.8% of patients (8 out of 165 patients) which were related to the platinum chemotherapy. Among 8 patients with thromboembolic events, 3 patients developed venous pulmonary thromboembolism and 5 patients developed cerebral infarction, out of which 4 had arterial cerebral infarction and one patient had a superior sagittal sinus thrombosis. All eight patients were symptomatic and one patient with cerebral infarction died because of the infarction. The majority of events (7 out of 8) occurred within the first 100 days of starting platinum chemotherapy. Overall, the median time until occurrence of a thromboembolic event was 24 days (range, 8 to 129days). None of the presumed risk factors associated with thrombosis were found be related to the occurrence of TEs on univariate analysis.
Conclusion:
The incidence of thromboembolic events were 4.8 % in our study was low due to the use of carboplatin-based regimens in the majority of patients. The majority of thromboembolic events occurred within 3 months from the initiation of chemotherapy.
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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: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-027 - Comparative Longitudinal Toxicity Analysis of EGFR Mutated NSCLC Treated with Either Pemetrexed Carboplatin or Gefitinib (ID 8967)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
Toxicity analysis in randomized studies is classically reported as maximum grade toxicity occurring during the course of treatment. Unfortunately, the duration of toxicity is neglected. Patients receiving targeted therapy like gefitinib frequently have low grade continuous toxicities. Longitudinal toxicity analysis may be a more appropriate method of quantifying and comparing toxicity.
Method:
EGFR mutated NSCLC patients treated with gefitinib or pemetrexed-carboplatin as a part of randomized study were selected for this analysis. Patients were evaluated on the 7th day after the start of therapy and then on days 15, 21, 42, 63, 84,105 and then subsequently every 2 months till progression. Toxicities in accordance with CTCAE version 4.02 occurring during each visit were documented at each visit. Three toxicities were selected for this analysis and these were diarrhea, skin rash and fatigue. R software was used for analysis. Maximum grade toxicity and longitudinal time -toxicity analysis was performed. Toxicities were compared between the 2 arms using both methods.
Result:
Among the 290 patients, half each were randomized to gefitinib and pemetrexed-carboplatin arm respectively. Any grade diarrhea was seen in 22 % of patients receiving gefitinib as opposed to 12% receiving pemetrexed-platinum (p-0.12%). Similar higher proportion of toxicity was seen in gefitinib arm for skin rash (33% versus 13%, p-0.00).The proportion of fatigue in gefitinib and pemetrexed -platinum arm were similar (6% versus 9%, p-0.59). The longitudinal time-toxicity analysis revealed that both rash and diarrhea were higher and more sustained in gefitinib arm. The difference area under the curve for rash and diarrhea were 10 units (p-0.192) and 21.89 units (p-0.09) respectively. The fatigue was similar in both arms (p-0.779)
Conclusion:
Longitudinal time -toxicity analysis provides information which is clinically relevant and might impact patients quality of life and hence should be performed in patients receiving targeted therapies.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-076 - QTWiST Analysis to Compare the Benefit of Gefitinib Versus Pemetrexed Platinum for Patients with EGFR Mutated NSCLC (ID 10431)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
In an open-label, Phase 3 randomized study (Clinical trial registry of India: CTRI/2015/08/006113), Gefitinib was found to be superior to Pemetrexed-Platinum in terms of progression-free survival in patients with EGFR mutated NSCLC. In this analysis, we aimed to assess the benefit of gefitinib over Pemetrexed platinum using quality-adjusted time without symptom or toxicity analysis method.
Method:
In this phase III, randomized study EGFR activating mutated patients were randomized in 1:1 fashion to either receive pemetrexed-carboplatin followed by maintenance pemetrexed or gefitinib till progression. Patients post progression received the treatment received in other arm if they were fit. These patients were followed up until death. Toxicity during the whole course of treatment was documented in accordance with CTCAE version 4.02 criteria. For QTWiST analysis, the overall survival and progression-free survival were documented. The overall survival was partitioned in 3 health states. These were TOX, TWiST, and REL. TOX state comprised of time in months spent by the patient in grade 2 or above toxicity post randomization but before the first progression. TWiST state comprised of time in months spent by the patient post randomization but before the first progression without grade 2 or above toxicity. REL state was defined as the time in months spent post the first progression until death. RStudio will be used for analysis. The data will be censored for this analysis on 30th June 2017. The restricted mean of all three health states would be calculated using non-parametric 500 boot straps. The time spent in each state will be weighted by a corresponding health-state utility coefficient for QTWiST calculation. A threshold utility analysis will be performed using utility values between 0-1. Where 0 represents a health state similar to death and 1 represents a perfect health state.
Result:
The restricted mean health state duration in months for each state with its 95% CI for each arm, the difference between the 2 arms for each health state with its 95%CI and corresponding p-value will be provided. The results of threshold utility analysis with the corresponding QTWiST difference between the 2 arms with p-value would be presented.
Conclusion:
LBA: Not applicable
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-015 - ROS-1 Rearranged Non Small Cell Lung Cancer and Crizotinib: An Indian Experience (ID 9315)
09:30 - 09:30 | Author(s): A. Joshi
- Abstract
Background:
ROS1 is a receptor tyrosine kinase that belongs to insulin receptor family.It acts as a driver oncogene in 1 to 2% of NSCLC patients. ALK and ROS1 Kinase domain share 77% amino acid identity within the ATP-binding sites. Crizotinib binds with high affinity to both ALK and ROS1, Crizotinib is approved for patients with the ROS1 translocation including those who have received chemotherapy and those who are treatment naive. This is based on a phase 1 expansion study which enrolled 50 patients with ROS1 rearrangement. Over 80 percent of patients had received one or more prior chemotherapy treatment regimens. The objective response rate was 72 percent. The median duration of response was 17.6 months, and the median progression-free survival was 19.2 months.A retrospective series from Europe which included 32 patients reported 80% response rates and a PFS of 9.1 months.In this paper, we report our experience with ROS1 rearranged NSCLC from India.
Method:
Advanced NSCLC with the presence of ROS1 fusion (FISH) patients whose demographic data were retrieved from prospective lung cancer audit database Response by RECIST 1.1 criteria, side effects using CTCAE v 4.02
Result:
Among 11 patients more than 1/4[th] of patients had PS of ≥2. Nearly 1/2 of patients had comorbidities and extrathoracic disease while none with brain or adrenal metastasis.Eight received platinum-based doublet chemotherapy, two oral EGFR TKI, and one upfront crizotinib. Four patients among those who received platinum doublet were subsequently exposed to crizotinib Among the 4 patients platinum-based doublet, 2 (PR)and 2 (SD).Out of 5 patients who received crizotinib, 3 patients experienced grade ½ fatigue and grade ½ vomiting. Grade ½ transaminitis, visual symptoms, grade ½ diarrhea, grade ½ neutropenia and asymptomatic bradycardia, grade ½ neutropenia and thrombocytopenia were seen in 1 patient each. Out of 8 patients who received chemotherapy 3 patients had grade ½ anemia, grade ½ vomiting. There was one mortality in non-crizotinib group.Out of 5 patients who received crizotinib, 4 patients had PR (80%).With a median follow-up of 9 months, median PFS and OS were 5.4 months and 8.5 months respectively for the entire cohort.Median PFS and OS was not reached for those who received crizotinib compared to median PFS of 2.5 months and median OS of 4.2 months(<0.01).Estimated 1 year OS was 80% for those who received crizotinib and 18% for who did not.
Conclusion:
In conclusion, Crizotinib is effective with acceptable side effect profile in patients with ROS1 rearranged NSCLC in our population
