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Sanjay Popat
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.09 - Isotoxic Dose-Escalated Radiotherapy (RT) in Non-Small Cell Lung Cancer (NSCLC) with Deep Inspiration Breath Hold (DIBH) (ID 10052)
12:00 - 12:05 | Author(s): Sanjay Popat
- Abstract
- Presentation
Background:
With interest in the use of isotoxic dose-escalated RT in treatment of inoperable NSCLC, this study investigated the impact of DIBH using the Active Breathing Coordinator™ (ABC- Elekta, Stockholm, Sweden) device on isotoxic dose escalation potential.
Method:
Following informed consent, a four-dimensional (4D) planning CT scan and a DIBH scan using the ABC device were acquired in patients sequentially in the same session. A motion-encompassing target volume on the 4D scan and a motion-managed target volume on the DIBH scan were created. The RayStation radiotherapy treatment planning system (research version 5.99.0.16) was used to generate two corresponding volumetric modulated arc therapy (VMAT) plans for each patient, following the guidelines of the isotoxic IMRT trial (NCT01836692). The target dose was escalated up to a maximum of 79.2 Gy in 44 twice daily fractions and plans optimised to minimise dose to normal tissues. Potential to escalate target dose and differences in dose-volume metrics between the plans were compared using the Wilcoxon signed-rank test.
Result:
21 patients were included. The mean total lung volume was significantly higher with DIBH compared to 4D scans with an increase of 44.7 % ± 17.4 % (mean ± standard deviation), p < 0.001). In 20/21 patients, the maximum target dose of 79.2 Gy was achievable in both plans, however in one patient 61.2 Gy was achieved with 4D compared to 75.6 Gy with DIBH planning. In the 20 patients achieving equivalent target dose-escalation, the mean lung dose was 17.0 Gy (± 0.3Gy ) with 4D versus 14.6 Gy (± 0.3 Gy) with DIBH (p < 0.001). There was a significant mean reduction in heart dose between the DIBH compared to 4D plans of 0.3 Gy (± 0.2 Gy, p< 0.001) and significant reductions in heart D100 %, D66 % and D33 %(p < 0.01). Mediastinal envelope and oesophageal doses were similar using both techniques.
Conclusion:
The use of DIBH compared to 4D planning aids lung and cardiac sparing in isotoxic dose escalated RT and for a small number of patients may allow an increase in target dose. Particularly given the interaction between lung and cardiac toxicity in locally advanced NSCLC treated with radical RT, use of DIBH for treatment may lead to a reduction in toxicity compared to a 4D approach. In acknowledgement of the use of a mid-ventilation technique in some institutions, comparison with this method is planned.
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.03 - Nintedanib + Pemetrexed/Cisplatin in Malignant Pleural Mesothelioma (MPM): Phase II Biomarker Data from the LUME‑Meso Study (ID 8111)
11:10 - 11:15 | Author(s): Sanjay Popat
- Abstract
- Presentation
Background:
Nintedanib is a triple angiokinase inhibitor. LUME-Meso (NCT01907100) is a randomised, Phase II/III study of ≤6 cycles of nintedanib+pemetrexed/cisplatin versus placebo+pemetrexed/cisplatin, followed by nintedanib or placebo maintenance, in chemo-naïve patients with MPM. In Phase II results, nintedanib+pemetrexed/cisplatin improved progression-free survival (PFS) versus control (hazard ratio [HR]=0.54; p=0.010), with a trend for prolonged overall survival (OS; HR=0.77; p=0.319). Benefit was most pronounced in patients with epithelioid tumours. Since no pharmacodynamic/predictive biomarkers are validated for anti-angiogenic therapies, exploratory analyses were conducted to investigate potential associations of plasma-derived angiogenic factors and genomic markers with treatment outcome in the LUME-Meso Phase II epithelioid population.
Method:
Blood samples were collected at baseline and, for patients receiving maintenance, at monotherapy Cycle 3 (C3mono) and end of monotherapy (EoTmono). Analyses focused on 58 angiogenic factors (Human AngiogenesisMAP[®] panel, Myriad RBM) and single-nucleotide polymorphisms (SNPs) in genes implicated in mesothelioma and/or associated with response to anti-angiogenic therapies in other tumour types (VEGFR1, VEGFR3 and mesothelin). Associations of biomarkers with treatment effect were evaluated by Cox regression and tested for interaction with false discovery rate (FDR) adjustment. Adjusted mean changes in angiogenic factor levels were compared between arms by ANCOVA. Analyses were exploratory, limited by small sample size, and considered hypothesis generating.
Result:
Of 77 patients with epithelioid tumours, angiogenic factor and genomic data were available for 71 and 67 patients, respectively. PFS/OS benefit of nintedanib appeared potentially more pronounced in patients with baseline plasma endoglin level below the median. There were possible weak associations between major homozygous genotypes for two VEGFR3 SNPs (rs307821 G/G and rs307826 A/A), and OS benefit and between VEGFR1 SNP rs9582036 A/A genotype and PFS benefit. Biomarker treatment associations were limited by small subgroup size, especially for low-frequency SNPs, and interaction tests were not significant after FDR adjustment. Regarding pharmacodynamic effects, adjusted mean change in interleukin-8 levels with nintedanib was greater from baseline to C3mono and lower from C3mono until EoTmono, compared with placebo. Nintedanib showed lower adjusted mean changes versus placebo for VEGFR2 from baseline to C3mono, and for VEGFR2 and VEGFR3 from baseline to EoTmono.
Conclusion:
These analyses represent the first biomarker results for nintedanib-treated MPM. While there seemed to be signals for greater PFS and OS improvement in patients with low plasma endoglin and major homozygous VEGFR1/3 genotypes, no biomarkers showed clear significant association with treatment benefit. These findings warrant further evaluation in the Phase III study.
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MTE 09 - Management of Difficult Symptoms (Sign Up Required) (ID 558)
- Event: WCLC 2017
- Type: Meet the Expert
- Track: Nursing/Palliative Care/Ethics
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 07:00 - 08:00, Room 503
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MTE 09.02 - Symptom Experiences and Symptom Clusters in Advanced Lung Cancer (ID 7788)
07:30 - 08:00 | Presenting Author(s): Sanjay Popat
- Abstract
- Presentation
Abstract:
Advanced lung cancer is characterized by a number of debilitating symptoms from the disease itself and also potentially its treatment. Toxicities from systemic therapies undoubtedly contribute significantly to patient experiences. For patients with oncogene-addicted lung cancer, long-term treatment is now considered routine given the excellent outcomes with EGFR, ALK, and ROS1-directed therapies. Nevertheless, toxicities from therapies can be debilitating often requiring dose reduction. Whilst toxicities for EGFR-directed therapy are common, variation between agents used contributes to differences in tolerability and rates of grade 3-4 adverse events, ranging from 29-42%. Moreover, whilst variation in rates of serious class-specific adverse events eg diarrhoea are again observed, most data is limited to patients suitable for randomization against chemotherapy and performance status (PS) 0/1, whilst the majority of patients with lung cancer have comorbidities and poorer PS. Thus, the TIMELY trial of afatinib in EGFR mutant non-small cell lung cancer (NSCLC) patients with comorbidities that precluded use of chemotherapy identified a grade 3 or more toxicity rate of 59%, considerably more frequent than in other studies of afatinib. Moreover, the management of tyrosine kinase inhibitor (TKI)-associated toxicities has been poorly investigated with limited data suggesting that prophylaxis improves cutaneous toxicities, and that further investigating additional causes of diarrhea can be beneficial. The implementation of immune-checkpoint inhibitors into routine clinical practice has markedly changed survival for those that respond. Nevertheless, such therapies can be associated with marked toxicities, with grade 3-5 toxicities seen in around 20% of patients, and immune-related toxicities seen in 11-16%, from pooled data, with a slight excess in pneumonitic events with PD1 inhibitors. These drugs result in a different spectrum of patient symptoms reported principally from immune-related adverse events (irAEs). Nevertheless, the reporting of irAEs in the literature is generally suboptimal for onset, management, and reversibility. The recognition of irAEs is key to optimal management and maintaining quality of life, with consensus around management of irAEs with international guidelines. Such symptom experiences and their temporal change can be measured through use of health-related quality of life measures or patient-reported outcome measures (PROMs). These include the EORTC-QLQ-C30 questionnaire, dividing symptoms into 4 domains, and is supplemented by the lung cancer-specific module QLQ-LC13 evaluating 133 items. These two latter instruments are the commonest used in lung cancer populations. The FACT-L questionnaire is another popular module, specific to lung cancer by modifying the original FACT-G module. Finally, the Lung Cancer Symptom Scale (LCCS) is a highly popular brief inventory analyzing the functional and physical aspects of lung cancer symptoms on routine quality of life. The implementation of PROMs into routine clinical care has been shown to impact on improving communication, patient satisfaction, and potentially outcome. Whilst tools for evaluating PROMS are previously validated, no tool has yet been prospectively validated for immune-checkpoint inhibitor therapy, with efforts currently ongoing. Nevertheless, current trial data using established PROMs measures suggests improvements in many quality of life domains for patients receiving immune-checkpoint inhibitor therapy compared to chemotherapy.
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OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)
- Event: WCLC 2017
- Type: Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:M. Chida, Jhingook Kim
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 311 + 312
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OA 03.02 - Comprehensive Characterization of Thymic Epithelial Tumour Subtypes Through an Analysis of Somatic Mutations and Copy Number Alterations (ID 10322)
11:10 - 11:20 | Author(s): Sanjay Popat
- Abstract
- Presentation
Background:
Thymic epithelial tumours (TETs) are rare and under-researched intrathoracic cancers. So far the only significant finding is a recurrent (43%) missense mutation in GTF2I. In addition to validating this finding, we set out to expand our understanding of the molecular changes underlying TETs through whole exome sequencing (WES) and detection of copy number alterations (CNAs) following SNP genotyping.
Method:
WES was performed on 17 TETs (2AB, 1B1, 3B2, 2B3, 6CA and 3NETT) and matched normal tissue. Somatic single nucleotide variants (SNVs) were identified with the GATK HaplotypeCaller and annotated for impact prediction (SnpEff 3.6b and SnpSift 1.3.4b) and population frequency (SnpSift 1.3.4b). The frequency of the GTF2I mutation was assessed with Sanger sequencing with semi-nested primers on DNA from 144 TETs of all subtypes. SNP genotyping was performed on 100 TETs of all subtypes with matched normal tissue in most cases, to identify somatic CNAs. Analysis was performed with ASCAT (v2.4.4) and copy number segments were annotated with Bedtools (v2.26.0).
Result:
WES confirmed a low mutation burden for TETs. No highly recurrent mutations were found. Hotspot mutations in NRAS and KRAS were seen, as was a hotspot mutation in TP53 in a NETT. A high impact frameshift MSH6 somatic mutation was noted in one of the squamous cell carcinomas (SCCs). Another SCC had a germline BAP1 mutation and a family history of other cancers, suggesting a BAP1 familial cancer predisposition syndrome in this individual. The GTF2I mutation was seen in 48 of 141 evaluable TETs (34%) and was present more commonly in type A (90%) and AB (69%) thymomas. The frequency decreased to 16%, 6% and 13% in B1, B2 and B3 thymomas respectively and was not seen in any squamous (0/12) or neuroendocrine carcinomas (0/6). Overall, the most frequent copy number gains in TETs involved chromosomes 7q (22%), 1q (17%) and 11q (17%). The commonest gain was in a gene not previously found to be amplified in solid tumours. The most frequent copy number losses were in chromosomes 6p (40%), 2q (37%) and 7q (32%). Gains and losses demonstrated distinct patterns between aggressive versus indolent subtypes.
Conclusion:
The mutation in GTF2I remains the single most frequently recurrent mutation in TETs. We are in the process of establishing a clinical use for this finding. Results from WES and CNA through SNP genotyping have provided important insight into other potential key players in the aetiology of this intriguing malignancy.
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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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P1.03-029 - Study of Plasma Homocysteine as a Marker of Toxicity and Depression in Patients Treated with Pemetrexed-Based Chemotherapy (ID 8643)
09:30 - 09:30 | Author(s): Sanjay Popat
- Abstract
Background:
Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine levels reflect folate deficiency and are suppressed by supplementation. Depression is common in lung cancer patients. Elevated homocysteine levels are linked to neurotoxicity; its association with depression is less clear.
Method:
This prospective observational study of 112 lung cancer patients receiving pemetexed-based chemotherapy assessed homocysteine level after 3 weeks of vitamin B12 and folate supplementation, hypothesizing that high levels reflect an ongoing deficiency and would correlate with increased chemotherapy toxicity and depression. All patients received B12 and folate supplementation and had a homocysteine level checked 3 weeks later. The primary objective was proportion of patients with a treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, between patients showing normal plasma homocysteine (i.e. successfully supplemented, SS group) and patients showing high levels (i.e. unsuccessfully supplemented, US group). Secondary objectives included grade 3-4 toxicity, overall survival and exploratory analyses for depression.
Result:
100 patients were included in the primary end-point analysis. 84% of patients demonstrated appropriate supplementation (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in the SS group was 44.0% (37/84) (95% confidence interval [CI] 33.2% to 55.3%) and in the US group was 18.8% (3/16) (95% CI 4.0% to 45.6%) (p=0.093). Proportion of patients experiencing grade 3-4 toxicity in SS group was 14.5% (95% CI 7.7% to 23.9%) and in US group was 18.8% (95% CI 4.0% to 45.6%) (p=0.705). The proportion of patients with a Hospital Anxiety and Depression (HAD) score >7 (indicative of depression) in the SS group was 63.9% (95% CI 46.2% to 79.2%) and in the US group was 75% (95% CI 34.9% to 96.8%) (p=0.695). Median overall survival was 11.8 months (95% CI 8.6 – 16.5 months) in the SS group and 8.8 months (95% CI 6.6 – 16.2 months) US group (Log Rank test; p-value = 0.484).
Conclusion:
Standard vitamin supplementation was adequate in the majority of patients and thus our US population was small. Homocysteine levels at 3 weeks did not correlate with increased toxicity or overall survival and is unlikely to be useful to identify patients at an increased risk of toxicity, though analysis was limited by the smaller than expected number of patients in the US group. Depression is very common in this population, and HAD score is a feasible assessment tool in this patient group.
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P1.09 - Mesothelioma (ID 695)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.09-011 - LUME-Meso Phase II/III Study: Nintedanib + Pemetrexed/Cisplatin in Chemo-Naïve Patients with Malignant Pleural Mesothelioma (ID 7937)
09:30 - 09:30 | Author(s): Sanjay Popat
- Abstract
Background:
Pemetrexed/cisplatin is the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM), with median overall survival (OS) of ~1 year. Nintedanib is a triple angiokinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3, platelet-derived growth factor (PDGF) receptors α/β and fibroblast growth factor receptors 1–3. VEGF and PDGF overexpression are associated with poor prognosis in MPM, and nintedanib has demonstrated efficacy in preclinical MPM models. Nintedanib also targets the Src and Abl kinases, which are involved in MPM cell migration. A randomised Phase II trial of nintedanib or placebo + pemetrexed/cisplatin in MPM followed by maintenance nintedanib or placebo, with progression-free survival (PFS) as the primary endpoint, was performed. With regulatory authority guidance, the Phase II data were unblinded. At the primary analysis, PFS benefit was observed with nintedanib, and confirmed at the updated analysis (hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.33–0.87; p=0.010; median PFS: nintedanib 9.4 months vs placebo 5.7 months). A strong signal towards improved OS also favoured nintedanib (HR=0.77, 95% CI: 0.46–1.29; p=0.319; median OS: 18.3 vs 14.2 months). The study was expanded to include a confirmatory Phase III part based on the primary PFS results, and the Phase II data assisted in planning of the Phase III part, including sample size estimation. Nintedanib was granted US Food and Drug Administration orphan drug designation for the treatment of MPM in December 2016.
Method:
The Phase III part of the study (NCT01907100) is currently recruiting participants. Four hundred and fifty chemotherapy-naïve patients worldwide (~140 sites in 27 countries), aged ≥18 years with unresectable MPM of epithelioid histology and Eastern Cooperative Oncology Group performance score 0–1 will be randomised 1:1 to receive up to six 21-day cycles of pemetrexed (500 mg/m[2])/cisplatin (75 mg/m[2]) on Day 1 + nintedanib or placebo (200 mg twice daily, Days 2–21), followed by nintedanib or placebo monotherapy until disease progression or undue toxicity. The primary endpoint is PFS with the key secondary endpoint being OS. An adaptive design will be used at the time of the primary PFS analysis to reassess the number of OS events for sufficient OS power. Other secondary endpoints are objective response and disease control (using modified Response Evaluation Criteria in Solid Tumors). The frequency and severity of adverse events, as well as health-related quality of life, will also be assessed. An exploratory analysis of predictive/prognostic biomarkers is planned.
Result:
Section not applicable
Conclusion:
Section not applicable
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P1.17 - Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies (ID 703)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.17-019 - B7-H3 Protein Expression in Thymic Epithelial Tumour Subtypes and Its Association with PD-L1 and Clinical Characteristics (ID 10332)
09:30 - 09:30 | Author(s): Sanjay Popat
- Abstract
Background:
B7-H3 (CD276) belongs to the B7 immunoregulatory family that includes PD-L1. Its expression is associated with poor overall survival (OS) in a range of solid tumours but its expression in TETs is unknown. Phase II clinical trials with anti-PD-1 inhibitors are on-going and exhibit good efficacy although they are often complicated by severe autoimmune toxicities. We measured the levels of B7-H3 in TETs and associated them with PD-L1 levels, OS and GTF2I status.
Method:
TMA sections from each of 125 TET FFPEs and 18 thymic hyperplasias were stained separately with antibodies to PD-L1 (clone 28-8, Abcam) and B7-H3/ CD276 (clone 6A1, Abcam). CD45 and cytokeratin (MF116) stains were used to differentiate epithelia and lymphocytes. All sections were scored with an H-score, giving a final score range of 0-300. For each antibody scores for each TET subtype were compared to each other with the Mann-Whitney test. Positive staining was defined as any staining above 0. Associations between the antibody scores and clinicopathological variables were determined.
Result:
The histological breakdown of analyzed samples was 17 A, 4 MNT LS, 30 AB, 25 B1, 26 B2, 5 B3, 10 CA, 8 NETT and 18 hyperplasias. B7-H3 protein was detected in the epithelia of 110 of 125 TETs (88%) and in 15 of 17 hyperplasias (88%) (Subtype breakdown in Diagram 1). No link between OS and GTF2I mutations status (previously described) was found. B7-H3 and PD-L1 were co-expressed in 94 of 125 TETs (75%). Only 2 B1 TETs were negative for both. Figure 1
Conclusion:
B7-H3 protein is expressed in the large majority of TETs, being highest in A and AB thymomas followed by squamous and neuroendocrine carcinomas. Trials with anti-B7-H3 monoclonal antibodies are already underway and given these findings, patients with TETs are likely to be good subjects for these trials.
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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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P2.03-058 - Tiger-3: A Phase 3 Randomized Study of Rociletinib Vs Chemotherapy in EGFR-mutated Non-small Cell Lung Cancer (NSCLC) (ID 8395)
09:30 - 09:30 | Author(s): Sanjay Popat
- Abstract
Background:
Rociletinib, an oral, irreversible tyrosine kinase inhibitor (TKI), selectively targets activating mutations in EGFR and the acquired resistance mutation T790M and demonstrated antitumor activity in the phase 1/2 TIGER-X study (NCT01526928). Initial results are reported from the TIGER-3 study (NCT02322281) of rociletinib vs chemotherapy in EGFR TKI-resistant patients with EGFR-mutated NSCLC.
Method:
Eligibility criteria included: metastatic or unresectable, locally advanced, EGFR-mutated NSCLC; radiological progression on most recent TKI therapy; ≥1 line of platinum doublet chemotherapy. Patients were not selected based on T790M status. Patients (N=900) were to be randomized (1:1:1) to rociletinib 500 or 625 mg BID or investigator’s choice of chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). The primary endpoint was investigator-assessed progression-free survival (PFS) (RECIST v1.1); objective response rate (ORR) was a secondary endpoint. The rociletinib dosing groups were combined and compared with chemotherapy in a step-down procedure (patients with a centrally confirmed T790M mutation, followed by all randomized patients).
Result:
TIGER-3 enrollment was halted upon discontinuation of rociletinib development in NSCLC in 2016; therefore, target enrollment was not achieved. TIGER-3 enrolled 75 patients in the rociletinib groups [500 mg BID, n=53; 625 mg BID, n=22] and 74 in the chemotherapy group. Median age was 62 years, 69.1% had ECOG Performance Status of 1, 39.6% were Asian, 58.4% were female, and median number of prior therapies was 3. PFS and ORR data are presented in the Table. The most common adverse events (all grade; grade ≥3) in the rociletinib group were diarrhea (62.7%; 2.7%), hyperglycemia (58.7%; 24.0%), nausea (37.3%; 4.0%), fatigue (37.3%; 8.0%), and decreased appetite (37.3%; 0%) and in the chemotherapy group were nausea (27.4%; 5.5%), anemia (24.7%; 2.7%), and fatigue (24.7%; 9.6%).Outcome Centrally Confirmed T790MPositive Centrally Confirmed T790MNegative Intent-to-Treat Population* Rociletinib[†] (n=25) Chemotherapy (n=20) Rociletinib[†] (n=36) Chemotherapy (n=41) Rociletinib[†] (n=75) Chemotherapy (n=73) Median PFS, mo (95% CI) 6.8 (3.7–12.2) 2.7 (1.3–7.0) 4.1 (2.5–4.6) 1.4 (1.3–2.7) 4.1 (2.8–5.5) 2.5 (1.4–2.9) HR (95% CI) 0.570 (0.285–1.140); P=0.105 0.532 (0.322–0.878); P=0.011 0.609 (0.423–0.875); P=0.006 Confirmed ORR, n (%) [95% CI] 9 (36.0) [18.0%–57.5%] 3 (15.0) [3.2%–37.9%] 3 (8.3) [1.8%–22.5%] 2 (4.9) [0.6%–16.5%] 13 (17.3) [9.6%–27.8%] 6 (8.2) [3.1%–17.0%] *Includes patients with undetermined T790M mutation status. [†]Rociletinib 500 mg BID and 625 mg BID dose groups were pooled for the analysis. CI, confidence interval; HR, hazard ratio.
Conclusion:
Incomplete enrollment precluded hypothesis testing. However, the data show a trend toward longer PFS and higher ORR with rociletinib.
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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: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-049 - Early Clinical Predictors of Progressive Disease or Non-Response to PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer (ID 10256)
09:30 - 09:30 | Author(s): Sanjay Popat
- Abstract
Background:
Treatment with PD-1/PD-L1 inhibitors are now the standard of care for patients with advanced non-small cell lung cancer. PD-L1 expression, in addition to interferon score and tumour mutational burden, are predictive biomarkers, however early clinical predictive biomarkers are lacking.
Method:
Patients with NSCLC who received treatment with PD-1/PD-L1 inhibitors between 1 Jan 2014 – 31 Dec 2016 were retrospectively identified from electronic health records. Data was collected on patient, treatment and tumour characteristics. Discrete variables were compared using Fisher’s exact test. Odds ratios (OR) were calculated with 95% confidence intervals (CI) for significant associations, using contingency tables.
Result:
We identified 91 patients, with a mean age of 65 years, of whom 52% were male. The majority were ex-smokers (69.2%), followed by never smokers (23.1%). Non-squamous histology was seen in 59.3% of patients and 86.8% of the patients had ECOG performance status 0-1. The lactate dehydrogenase (LDH) at baseline, cycle 2, and the change-in LDH≥10% at cycle 2 and 6 weeks, did NOT predict for disease control rate (DCR) at the first tumour response evaluation (TRE). A LDH ≥ upper limit of normal at 6 weeks DID predict disease progression at the first TRE (P-value=0.04), with an OR of 3.58 (95% CI 1.11 – 11.52). The neutrophil-lymphocyte ratio (NLR) at baseline and 6 weeks, and the change-in NLR>10% at cycle 2 and 6 weeks did NOT predict for DCR at the first TRE. A NLR ≥5 at cycle 2 DID predict for disease progression at the first TRE (P-value=0.008), with an OR of 3.92 (95% CI 1.48 – 10.39). Receiver operator curve analysis of the early LDH/NLR score (1 point each for 6 week LDH ≥ upper limit of normal and cycle 2 NLR ≥5) predicted for disease progression at the first TRE (C-index 0.77, P-value <0.0001).
Conclusion:
The LDH greater than upper limit of normal at cycle 2 and NLR ≥5 at 6 weeks predicts for disease progression at the first TRE. These routine early predictive biomarkers could be used to identify non-responders when treating with PD-1/PD-L1 inhibitors prior to a CT scan. This data needs validation in a larger cohort.
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P3.12 - Pulmonology/Endoscopy (ID 728)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.12-003 - Optimised Inhaler Therapy Is Superior to Supportive Care Alone for Dyspnoea in Patients with Coexisting COPD and Lung Cancer (ID 9368)
09:30 - 09:30 | Author(s): Sanjay Popat
- Abstract
Background:
Breathlessness is a common, debilitating symptom associated with both COPD and lung cancer. Opiates remain the mainstay of treatment for breathlessness in oncology.
Method:
Lung cancer patients were prospectively enrolled in this single-centre, open-label, randomised controlled trial. Eligible patients met British Thoracic Society diagnostic criteria for COPD, had a visual analogue score (VAS) dyspnoea ≥ 4 and had other reversible causes for breathlessness excluded. Patients were randomly assigned (1:1) between the intervention arm of salbutamol 100 mcg, 2 puffs QDS and tiotropium 18 mcg OD +/- salmeterol 50 mcg/fluticasone 500 mcg 1 puff BD (if FEV~1~ <50% predicted) in combination with best supportive care (BSC) or to BSC alone (control). Control arm patients could continue on any short-acting bronchodilators and BSC included oral morphine and/or benzodiazepines. Patients underwent spirometry, 6 minute walk test (6MWT), VAS dyspnoea and quality of life questionnaires (QOLQ) at baseline and after 2 and 4 weeks. The primary endpoint was the proportion of patients with ≥ 2 point improvement in VAS dyspnoea at 4 weeks.
Result:
Among the intention to treat population (n=63), 53 patients (84%) had NSCLC and 10 (16%) had SCLC. The median baseline VAS was 7.1 and the median baseline FEV~1~ was 1.5L (63% predicted). The primary endpoint response rate (RR) was higher in the intervention group n= 32 [RR: 53% (95%CI 35% to 71%)] than in the control group n= 31 [RR: 26% (95% CI 12% to 45%) p = 0.02]. Figure 1 There were no statistically significant differences between the groups for change in 6MWT or QOLQ between baseline and the 4 week assessments.
Conclusion:
For patients with co-existing COPD and lung cancers, VAS dyspnoea is significantly improved by the addition of inhaled therapies to best supportive care. This study highlights the importance of diagnosing and treating COPD in all lung cancer patients.
