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Treatment of nonsmall cell lung cancer (NSCLC) carrying an epidermal growth factor receptor (EGFR) mutation depends on EGFR tyrosine kinase inhibitors (TKIs). However, all patients treated with EGFR TKI eventually develop progressive disease. Approximately, 20% of patients do not respond to EGFR TKIs, which is defined as primary resistance. The prognosis of these patients is similar to NSCLC with nondriver mutations. We report a case of a patient with EGFR exon 21 mutation who rapidly progressed in 15 days on Gefitinib. Next-generation sequencing (NGS) showed a MET exon 14 skip mutation coexisting with EGFR exon 21 mutation, causing primary resistance to EGFR TKI. Based on NGS reports, a treatment combining Gefitinib and Capmatinib, a MET inhibitor, induced a rapid response in the patient, which was sustained at the end of 8 months. This clearly emphasizes the need for comprehensive genomic profiling using NGS over single gene testing.

In order to overcome the polysorbate induced hypersensitivity reactions with chemotherapy drugs, novel drug-delivery mechanisms have been developed in the last decade. D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is formed by esterification of alpha-tocopheryl succinate and polyethylene glycol 1000.This was a real-world retrospective analysis designed to evaluate safety and efficacy of TPGS-docetaxel in various cancers. Patients hospitalized between June 2018 and May 2019 were included in the data set. While the efficacy was assessed by the Response Evaluation Criteria in Solid Tumors criteria, safety was assessed by the National Cancer Institute Common Terminology Criteria-adverse event (AE) criteria.A total of 61 patients who received at least one dose of TPGS-docetaxel were incorporated into the analysis set. The dose of TPGS docetaxel ranged from 20 mg/m2 to 120 mg/m2, commonly prescribed dose being 75 mg/m2. While 25 (40.98%) patients had a partial response, 17 (27.86%) patients had stable disease. Five (8.19%) patients progressed and 4 (6.55%) patients died during the chemotherapy, which was adjudicated to be unrelated to the drug as opined by the treating clinician. AE were reported in 42 patients in the safety data set. There were no AEs pertaining to hypersensitivity reported during the study. One AE of Grade 3 hand foot syndrome was encountered.The preliminary evidence suggests that the novel TPGS-based docetaxel formulation is efficacious in various cancers, and importantly, it has an enhanced safety profile, as it is devoid of polysorbate 80 induced hypersensitivity reactions.

e15021 Background: To analyze the role of Circulating tumor cells (CTC) as a confirmatory personalized biomarker for monitoring the disease progression, disease burden, and minimal residual disease in epithelial origin cancers. Methods: In this retrospective study, 127 patients with colorectal, breast, and ovarian cancer at stage III and IV were analyzed. The patients were at various stages of intensive chemo and radiotherapy while the CTCs were isolated and enumerated from 1.5 ml of blood. The decision to continue chemotherapy or change to oral metronomic therapy was based on the presence of circulating tumor cells in Stage III. While in stage IV, serial measurement of CTC guided therapy. CTCs were isolated using OncoDiscover platform possessing EpCAM antibody based immunomagnetic targeting of magnetic nanoparticles after RBC lysis. CTCs were imaged and identified as CK18+ and CD45- cells showing a well-defined nucleus using a motorized fluorescence microscope operational with a monochrome camera. CTCs were enumerated using automated image analysis software and counts were expressed as number per 1.5 ml of blood. Results: In this retrospective study we analyzed blood sample from 127 patients with the advanced stage epithelial cancers (breast- 50 %, ovarian -27 %, colorectal- 23 %) for the presence of CTCs. Amongst those, 52 % showed the presence of CTCs (breast- 52 %, ovarian -46 %, colorectal- 58 %). The CTC count ranged between 1-5 / 1.5 ml of blood with mean and median value of 2 and 1. Among the CTC positive population, majority had CTC count of 1 (44.4 %), while more than 2 CTCs were observed in 11 % of population. CTC clusters were detected in 13 % of population which predominantly were stage IV patients. 67 % among the follow up patients showed decrease in CTC count from the baseline due to the prescribed treatment, while 22 % patients showed increase in CTC count from the baseline. 11 % patients did not show change in CTC count from the baseline. When CTCs count was investigated as an independent variable to monitor the therapeutic response, it correlated well with the positive or negative outcome. In few representative cases, the reduction of CTC number from the basal value was indicative of an effective treatment. Exceptionally, in a representative colorectal cancer case, PET showed no primary as well secondary tumor burden, but the presence of CTCs in blood led further investigating an abdominal MRI that indicated multiple liver lesions suggesting micro-metastasis. Subsequent to SIRT treatment, the patient showed complete tumor regression and absence of CTCs in peripheral blood. Conclusions: Our data suggest that CTC can serve as a dynamic intermittent biomarker for monitoring the disease progression in advanced stages and assess the therapeutic response, thus emphasizing the role of CTCs in personalized cancer management.

3019 Background: Homologous recombination deficient (HRD) tumors are highly responsive to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. Pathogenic BRCA-1 and BRCA-2 (BRCA1/2) alterations are key members of the HR DNA repair pathway but genomic instability status, including loss of heterozygosity, telomeric allelic imbalance and large scale state transitions across the genome are also predictive of HRD. HRD testing is currently performed by next generation sequencing which can take 2-4 weeks for results, has a high failure rate, requires significant tissue and is costly. We developed and tested the ability of an AI enabled platform to predict HRD status from the analysis of whole slide imaging of the diagnostic H&E slide. This platform, iPREDICT-HRD is rapid, precise, and cost effective. Methods: The AI engine was trained on 120 H&E slides that were used to identify tumor prior to manual microdisseection for HRD assessment by NGS. Histopathological features were extracted, followed by feature mapping to predict HRD status based on the results of NGS testing. ResNet AI algorithm was trained to segment, annotate and predict HRD status. 10 lac tiles of 256x256 size at 40x magnification were generated per pathological class. 70% of the data set was used for training and 30% for validation of the AI model. Results: Using single blinded clinical samples, iPREDICT-HRD tool detected HRD + ve samples with 99.3% accuracy with 100% sensitivity and 99% specificity in the test set. Patch-level predictions of HRD status demonstrated intra-tumor heterogeneity within the H&E slides. Visual inspection of the heatmap suggested the presence of patches with high predictive ability of HRD status and this outperformed an average HRD score for slides with heterogeneity. Conclusions: AI-enabled prediction of HRD status can be accurately performed on diagnostic H&E slides potentially yielding results quickly and afforadably, even when limited tissue is available for testing.

e21034 Background: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) resulted in significant improvement in the outcomes of patients with activating EGFR mutations. But the ideal treatment of patients harboring uncommon, or compound mutations is not well defined. This multicentric audit was conducted to study the distribution, treatment pattern, and outcomes of patients with uncommon or compound EGFR mutations. Methods: This was a multicentric retrospective study that included patients with uncommon (mutations other than Exon 19 deletions and Exon 21 L858R) or compound (double or complex) mutations treated during the period of 2017-2020. Statistical analysis was done using SPSS version 20.0. Descriptive statistics were used wherever appropriate. Kaplan Meier Aanlaysis was performed for estimation of PFS and OS. Results: Total 99 patients with uncommon or compound mutations were included in the study. The median age was 55 years (25-82 years). Majority were males (n=65,67%) and 47 (47%) were smokers. Sixty-seven patients (68 %) had a single uncommon mutation and the remaining 32 (32%) had compound mutations. Most common mutations were exon 20 insertion (n=34, 35%) and T790M (N=16,16%). Other frequent mutations observed were exon 18 G719X (n=7,7%) and exon 21 L861Q (n=3,3%). Twenty-three patients (n=23,23%) were eligible only for best supportive care. Thirty-two patients (32%) received first-generation TKI, 30 patients (30%) received palliative chemotherapy and 11 patients (11 %) received Osimertinib. Gefitinib with chemotherapy was used in 2 patients and combination of Gefitinib with Afatinib was used in one patient. Overall response rate and clinical benefit rate with first line treatment was 23% and 35% respectively. Response could not be assessed in 14 patients. Median PFS was 5 months (95% CI 3.4-6.9) and median OS was 8.3 months (95% CI 3.3- 13). In patients who received any form of systemic treatment, median PFS was 6.2 months (95% CI- 3.3-9.1) and OS was 11 months (95% CI -8.9-13.9). Conclusions: The most frequent uncommon mutations in India are exon 20 insertion followed by compound mutations and exon 20 T790M mutation. Outcomes of patients with these rare mutations are dismal in the real world setting with the available treatment options.

e21201 Background: Osimertinib is one of the favoured treatment options in EGFR mutated NSCLC and was established as a treatment option in last 2-3 years. However the treatment pattern post-osimertinib failure is not established. Hence we conducted this audit to study the pattern of treatment post-osimertinib failure in India. Methods: This was a retrospective multi-centric audit of adult (age ≥18 years) EGFR mutated NSCLC patients who were treated with osimertinib and had failed. The treatment pattern of these patients was noted. Descriptive statistics were performed. Median with range was estimated for continuous variables while the percentage with 95% CI were estimated for ordinal and nominal variables. Results: We had 25 patients who had failed on osimertinib. Oligo-progression versus widespread progression was seen in 5 (20%) and 20 (80%) patients respectively. The median age was years 56.5 year (Range-26-71) with 4/25 (16%) of patients were elderly (≥65 years). Male-to-female ratio was 18:7 (72% males, 28% females).The ECOG PS at failure were 0-1 in 12 patients (48%), 2 in 11 patients(44%) and 3-4 in 2 patients (8%) patients. The treatment offered were platinum doublet in 14 patients (56%) with variable combinations with TKIs in 5 patients (20%) and bevacizumab in 4 patients(16%). A repeat NGS for assessing the mechanism of resistance was done in patients revealed new mutations in 6 patients (24%) with EGFR Exon 20 T790M being most common in 3 patients (12%). Conclusions: We conclude that, in real-world practice, platinum-doublet formed the backbone of treatment post-osimertinib progression, with variable combinations, most commonly, along with TKIs or bevacizumab. No standard guidelines for the treatment of patients post-osimertinib progression are available with variable responses and tolerability. Larger and prospective studies are needed to identify the best options of therapies in such patients.

e18718 Background: Comprehensive genomic profiling (CGP) assay, a next-generation sequencing (NGS) based technique generates a large amount of genomic information about a cancer. While CGP is increasingly used in low-middle income countries (LMIC), little is known about the extent to which these benefits patients. Here we describe the proportion of patients with advanced cancer in India who eventually receive targeted therapy for an actionable genetic alteration identified on CGP assays. Methods: This was a multicenter, retrospective cohort study in adult patients with advanced non-hematological malignancies who underwent a CGP test. We excluded patients who were identified to have a genetic alteration that has a well-validated targeted standard-of-care therapy (e.g.; EGFR exon 18, 19, 21 mutations for lung cancer, HER2 amplification for breast cancer). Participating oncologists provided anonymized information of consecutive CGP test reports through an online data capture form. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. Results: During 2019-20, 12 medical oncologists provided CGP reports for 297 patients; 235 met the inclusion criteria. Fourteen different testing panels were used by the oncologists. Among the study cohort, 45% were male. Eighty nine percent underwent tumor tissue biopsy and 11% had liquid biopsy. The most common cancers were lung (19%), breast (18%), pancreatobiliary (9%) and colorectal (6%). Patients received a median of 2 lines (range: 0-5) of prior systemic therapy. Based on the CGP assay, 35 patients (15%) received targeted therapy. Among them, 29% was for HER2 amplification (non-breast cancer), 26% for PIK3CA mutation, 11% for HER2 or EGFR exon 20 insertion mutation (lung cancer), 5% each for BRAF mutation (non-melanoma), EGFR mutation (non-lung cancer) and MET mutation. Conclusions: In a LMIC setting, 15% patients received a targeted therapy based on CGP assay. This is comparable to reports from high income countries. Considering the limited access to new drugs and clinical trials, this finding requires further analysis.

e14012 Background: Leptomeningeal carcinomatosis (LCM) is a rare event and has a dismal prognosis. Limited data is available from India on LCM. Hence we did this country wise audit of LCM. Methods: This was a retrospective, multicentric audit of adult (age ≥ 18 years) patients with diagnosis of LCM, conducted across India in 2020 for patients treated from 2010 to 2020. Baseline characteristics, previous treatments, cancer sites, LCM diagnosis details, treatment pattern and overall survival (OS) were collected. Descriptive statistics were performed and Kaplan Meier analysis was performed for estimation of OS. Results: We had 84 patients diagnosed with LCM. The diagnosis of LCM was confirmed in 52 (61.9%) and probable 32 (38.1%) patients. The mean age was 51.8 years (SD-10.8) and we had 46 (54.8%) females. The three most common site of malignancy were lung, breast and gastrointestinal with 45 (53.6%), 22 (26.1%) and 9 (10.7%) patients. The ECOG PS at the presentation of LCM was 1, 2 in and 3-4 in 41 (48.8%), 28 (33.3%) and 15 (17.9%) respectively. LCM was seen at diagnosis in 2 patients (2.4%) and at progression in rest. The status of the extracranial disease at the occurrence of LCM was progressive disease in 39 patients (46.1%). The treatment offered was best supportive care in 24 patients (28.6%), systemic therapy only in 27(32.1%), systemic therapy and intrathecal therapy in 22 (26.2%) and only intrathecal therapy in 11(13.1%). Among 33(39.3%) patients receiving IT methotrexate was used in 23 (27.4%) and the combination of methotrexate, AraC and hydrocortisone was used in 10 (11.9%). The CSF clearance rate was assessed in 24 (28.6%) patients and the clearance rate was 13.1% (n=11). The median duration of therapy was 4 weeks (IQR 1-14). The median os was 90 days (95% CI 46.2-133.8). Conclusions: LCM has a grave prognosis and nearly 1/3rd patients are treated with best supportive care. Intrathecal therapy though part of all guidelines is administered in 39% of patients. This data can serve as a benchmark for further improvement to facilitate studies for further improving the outcomes.

The management of patients with advanced non-small-cell lung cancer (NSCLC) is becoming increasingly complex, with the identification of driver mutations/rearrangements and the development and availability of appropriate targeted therapies. In 2018, a group of medical oncologists with expertise in treating lung cancers used data from the published literature and experience to arrive at practical consensus recommendations for the treatment of advanced NSCLC for use by the community oncologists. These recommendations were subsequently published in 2019, with a plan to be updated annually. This article is an update to the 2019 consensus statement. For updating the consensus statement, a total of 25 clinically relevant questions on the management of patients with NSCLC on which consensus would be sought were drafted. The PubMed database was searched using the following terms combined with the Boolean operator “AND:” (lung cancer, phase 3, non-small cell lung cancer AND non-small-cell lung cancer [MeSH Terms]) AND (clinical trial, phase 3 [MeSH Terms]) AND (clinical trial, phase iii [MeSH Terms]). In addition, “carcinoma, non-smallcell lung/drug therapy” (MeSH Terms), “lung neoplasms/drug therapy” (MeSH), clinical trial, phase III (MeSH Terms) were used to refine the search. The survey results and literature were reviewed by the core members to draft the consensus statements. The expert consensus was that molecular testing is a crucial step to be considered for patients with NSCLC at baseline, and in those who progress on first-line chemotherapy and have not undergone any prior testing. For mutations/rearrangement-negative patients who progress on first-line immunotherapy, doublet or single-agent chemotherapy with docetaxel and/or gemcitabine and/or ramucirumab should be considered. Patients who progress on the newer anaplastic lymphoma kinase inhibitors should be considered for second-line therapy with lorlatinib or systemic chemotherapy. Maintenance therapy with pemetrexed is preferred for NSCLC with non-squamous histology and should be avoided in NSCLC with squamous histology.

e12028 Background: The worldwide resurgence of interest in the epidemiology of lung cancer is due to the changing histological spectrum, global increase in non smokers, females and the introduction...

e12004 Background: Lung cancer in nonsmokers as a separate category ranks as the seventh most common cause of cancer deaths worldwide. This study aimed to identify clinically meaningful differences...