Virtual Library

Start Your Search

Kumar Prabhash



Author of

  • +

    P01 - Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics (ID 227)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P01.24 - Ramucirumab + Docetaxel (DOC) vs PBO + DOC for Stage IV NSCLC after Disease Progression (REVEL): Indian Sub-Group Analysis (ID 3526)

      00:00 - 00:00  |  Presenting Author(s): Kumar Prabhash

      • Abstract
      • Slides

      Introduction

      The REVEL study demonstrated improved survival of ramucirumab (RAM) plus docetaxel (DOC) as second-line therapy in patients with Stage IV Non-small cell lung cancer (NSCLC). We conducted an exploratory analysis of safety and efficacy in the Indian patient subgroup.

      Methods

      Adult patients with histologically or cytologically confirmed NSCLC (squamous and nonsquamous) who progressed after 1 prior first-line platinum-based therapy regimen were randomized to receive RAM + DOC or placebo (PBO) + DOC. Prior bevacizumab as first-line and/or maintenance therapy was allowed. The trial was stratified by ECOG PS (0 vs. 1), gender (female/male), maintenance therapy (yes/no), and geographic region (East Asia/Rest of the World). Kaplan-Meier methodology was used to estimate survival parameters. Overall Survival (OS), Progression-free survival (PFS), Objective Response Rate (ORR) and Disease Control Rate (DCR) were reported. Safety analyses were performed on all randomized patients who received any study treatment. Since this is an exploratory analysis, it is not powered for statistical testing and p-values are not reported.

      Results

      55 Indian patients were included in the REVEL study. Baseline characteristics and prior therapies were well balanced between treatment arms. 80% of patients had nonsquamous histology. 78.2% were male. All patients received prior standard platinum-based therapy: 25.5% maintenance, and 18.2% taxane (paclitaxel only) as part of first-line therapy. Median OS and PFS was increased for RAM + DOC as compared to PBO + DOC arm. Safety data showed that RAM + DOC is well tolerated by Indian patients, with similar rates for most treatment-emergent adverse events (TEAEs) between treatment arms.

      Efficacy and Safety Data

      RAM + DOC

      N=22

      PBO + DOC

      N=33

      OS median, months 13.5 5.3
      HR (95% CI) 0.53 (0.25-1.12)
      PFS median, months 5.6 1.5
      HR (95% CI) 0.49 (0.25-0.95)
      ORR, % 27.3 21.2
      DCR, % 68.2 36.4
      Patients experiencing at least 1 TEAE, any grade, % 100 93.8
      Grade ≥3 TEAEs, % 81.8 71.9
      Patients experiencing at least 1 serious TEAE, % 50 59.4
      TEAEs leading to the discontinuation of any study drug, any grade, % 9.1 3.1
      NB – Objective Response Rate (ORR): (complete response + partial response), Disease Control Rate (DCR): (CR+PR+ stable disease)
      Conclusion

      Indian patients enrolled in the REVEL study showed a trend of prolonged OS and PFS when treated with RAM + DOC compared to PBO + DOC. RAM + DOC appears to be well tolerated by Indian patients, albeit with a higher TEAE-related discontinuation rate.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P33 - Pathology - Immunotherapy Biomarker (ID 101)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P33.18 - The Prevalence of PDL-1 Expression in Lung Cancer: Real-World Experience from a Tertiary Care Oncology Centre (ID 2287)

      00:00 - 00:00  |  Author(s): Kumar Prabhash

      • Abstract
      • Slides

      Introduction

      Immune checkpoint inhibitors are the new key players in lung cancer management. Increasing demands for PD-LI(Programmed Death-Ligand 1) testing has been observed recently and its role is emerging as a potential biomarker for immunotherapy. However, there is the paucity of the Indian data on the prevalence of PDL1 expression. This study was undertaken with an objective to evaluate the prevalence of PD-L1 expression in lung cancer patients and analyze its correlation with clinicopathological factors

      Methods

      All cases of histologically proven lung cancer, diagnosed between January 2017–November 2019, wherein PD-L1 testing was performed were retrieved from electronic medical records. PDL-1 Testing was performed using rabbit Anti-Human PD-L1 monoclonal antibody(Ventana clone SP263) on VENTANA BENCHMARK XT Auto-immmunostainer. Membranous PD-L1 expression of >/ =1% in the tumour cells was regarded as positive. Prevalence of PD-L1 expression and its correlation with clinic-pathological factors were recorded. Further, stratification of the cases was done, in subgroups of: Negative PDL1 (0/<1% PD-L1 expression ), low PDL1 expression(1 – 49%) and high PD-L1 expression (> =50%). The intensity of expression was recorded as weak, moderate & Strong

      Results

      Out of total 627 clinical request for PDL1 testing in lung cancer during this period, the results could be analyzed in 568 cases(In 35 cases the test could not be performed due to inadequate tumour content and in 23 cases although the test was performed, but could not be interpreted due to technical and interpretative issues). Hence the study cohort comprised of 568 cases. The median age was 56.95 years (range: 29-83years) with male predominance (M:F ratio-2.4:1) and advanced clinical stage III/IV[482(84.8%)]. Smoking history was present in 340 cases(59%). Lung biopsies were the most common type of specimen (n=351,61.7%) followed by metastatic lymph nodes (n=101, 17.8%), effusion cytology cell block (n=36, 6.3%) liver (n=33,5.8%) and others metastatic sites (n=40, 7%). Adenocarcinoma was predominant histological subtype(n=437,76.9% ) followed by squamous cell carcinoma(n=87, 15.3% ), NSCLC(n=13, 2.28%), small cell carcinoma (n=12, 2.11% ) and others(n=19,3.34%).

      Overall 57.5 %(n=327/568) of cases revealed PD-L1 positivity(> 1% expression of any intensity) including low PDL1 expression (1-50%) in 37.6 %(n=214)and high PDL1 expression(>50%) was seen in 19.8%(n=113). Almost one-third of positive cases (n=110/327, 33.6%), the PDL1 expression was very low i.e. < 10 % of tumour cells. Most of the cases revealed IHC expression of moderate-intensity (n=160, 48.9%) followed by weak(n=85,26%) and strong intensity in 82 cases(25%). Heterogeneous expression was noted in 74 cases (22.6%). The expression was greater in tumours with squamous histology, smokers and female patients. Further, PDL-1 positivity rates were higher in EGFR mutated tumors70/124(66.7%) as opposed to EGFR wild tumours 224/362(41.9%)

      Conclusion

      This was the first comprehensive study on the prevalence of PD-L1 expression in Indian lung cancer population demonstrating real-world data. Although the overall positivity rate of PD-L1 expression was 58%, only 19% of cases had high expression i. e in > 50 % tumour cells. Heterogeneity in PD-L1 staining is a crucial factor affecting its evaluation. The findings reinforces the utility of PDL1 testing in Indian patients for segregation of patients for frontline immune checkpoint inhibitors

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P37 - Pathology - Biomarker Testing (ID 107)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P37.14 - Comparative Evaluation of IHC versus FISH for Detection of ROS1 Fusion in Lung Cancer (ID 2135)

      00:00 - 00:00  |  Author(s): Kumar Prabhash

      • Abstract
      • Slides

      Introduction

      ROS1 gene rearranged tumours are a rare, yet distinct molecular subgroup of non-small cell lung carcinomas (NSCLC). This study was performed in order to determine the comparative diagnostic accuracy of ROS1 immunohistochemistry(IHC), as opposed to Fluorescence in situ hybridization(FISH) for its ability to detect ROS1 gene rearrangement in NSCLC.

      Methods

      A validation study designed to assess the diagnostic accuracy of ROS1 IHC using D4D6 (Cell Signaling Technology (CST), Danvers, MA) antibody clone for detection of ROS 1 gene rearrangement as compared to FISH testing using ZytoLight SPEC/ROS1 Dual-Colour Breakapart Probe(ZytoVision, Bremerhaven, Germany) was performed, on an enriched cohort of ROS1 rearranged tumours(including 44 ROS1 rearranged and 166 ROS1 non-rearranged cases). The IHC interpretation was performed by two pathologists independently, who were blinded to the FISH results. Receiver operating characteristics (ROC) curves were used to determine the optimal cut-off value for H-score and proportion of positivity for ROS1 IHC, in order to discriminate between patients with ROS1-rearranged and ROS1- non-rearranged tumours.

      Results

      Overall ROS1 IHC positivity was observed in 41/210 (19.52%) and 40/210 cases (19.05%) by two different observers, independently, blinded to FISH results, with the almost perfect interobserver agreement [ Kappa value 0.985. (95%CI, 0.95 to 1)]. The immunoexpression was predominantly cytoplasmic and heterogenous with median H-score of 165(range 5-300). Amongst, 44 ROS1gene rearranged cases, 40 cases were positive by ROS1 IHC and amongst, 166 ROS1gene non-rearranged cases, 165 cases were negative by ROS1 IHC. Hence, overall ROS1 IHC had a sensitivity of 90.9%, a specificity of 99.40%, the positive predictive value of 97.56% and negative predictive value of 97.63% considering FISH as the gold standard. A total of 5 discordant cases including one false positive(ROS IHC+/FISH-) and 4 false negatives (ROS IHC-/FISH +) were recorded. ROC curve analysis revealed the optimal cut-off: H-score of ≥2.5 and proportion of positivity ≥2.5%, can best predict the ROS rearrangement using ROS IHC in this study cohort. In 6 cases, of ROS1 rearranged tumours, low IHC expression(i.e only weak intensity staining (1+), positivity in <25% tumour cells and H-score <100) was noted. Although, 3 out of these 6 patients had received the Crizotinib, however, the clinical response was not as promising and developed progressive disease, after a short interval of Crizotinib.

      Conclusion

      The comparative evaluation in this enriched ROS1 rearranged cohort was unique in term of high specificity(99.40%), and relatively low sensitivity(90.9%) of ROS1 IHC and are somewhat contradictory as compared to previous reports. None of the previously reported cut-off criteria (H score ≥100/150, Staining intensity of ≥2+ in 30% tumour cells) can predict the ROS1 rearrangements with 100%accuracy in our study population and, some cases might be devoid of further molecular testing. Hence, it raises concerns about the utility of D4D6 antibody clone for ROS1 screening. Use of the appropriate cut off interpretative criteria’s can maximize the sensitivity and specificity of ROS1 IHC for predicting the ROS1 rearrangements. The corelation of the level of ROS1 protein expression with response to the Crizotinib needs to be evaluated further.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P76.26 - Survival Outcomes in Patients Receiving Second Line Osimertinib Post First Line First Generation TKI Alone or in Combination with Chemotherapy (ID 1372)

      00:00 - 00:00  |  Author(s): Kumar Prabhash

      • Abstract
      • Slides

      Introduction

      Although osimertinib is recommended as first line therapy in patients with EGFR mutated NSCLC, the cost and limited availability in developing countries prohibits its widespread use. Osimertinib is the standard of care second line anti EGFR therapy in non small cell lung cancer (NSCLC) who develop exon 20 T790M mutation post progression on first generation TKI. With recent evidence of efficacy of first generation TKI plus chemotherapy combination as effective first line therapy in EGFR mutated NSCLC, it is not known whether second line osimertinib leads to different outcome.

      Methods

      We retrospectively analysed data of patients from the study of gefitinib (Gef) vs gefitinib plus chemotherapy (GC) who progressed after first line therapy and were found to harbour exon 20 T790M mutation in repeat biopsy or cell free DNA samples and received Osimertinib as second line therapy. We compared progression free survival (PFS) and overall survival (OS) on 2nd line Osimertinib in patients who received Gefitinib versus Gefitinib plus Pemetrexed Carboplatin as 1st line chemotherapy.

      Results

      A total of 65 patients received osimertinib in the second line settings out of which 58 were analysable. There were 30 males and 28 females. The median age of cohort was 53 years (range 38-72). The median followup duration was 10 months. Median PFS on osimertinib in patients who received Gef (n=35) as first line therapy was 9 months (95% CI: 5.5-12.5) while for patients of GC arm, it was 8 months (95% CI: 4.8-11.2), p=0.483.. The corresponding median OS was 12 months (95% CI: 8.1-15.9) and 17 months (95% CI: 5.5-28.5), p=0.353.

      Conclusion

      There was no statistically significant difference between PFS and OS on second line osimertinib for patients who received first line first generation TKI alone or in combination with chemotherapy.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P82 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Radiotherapy (ID 259)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P82.03 - Immunotherapy in Combination with Hypofractionated Radiotherapy for Lung Cancer: A Real-World Experience (ID 2238)

      00:00 - 00:00  |  Author(s): Kumar Prabhash

      • Abstract
      • Slides

      Introduction

      A better understanding of immune mechanisms at the molecular and cellular levels has thrown light on the complex interactions between tumor, radiation and the immune system. Clinical studies have confirmed the synergy between immune checkpoint inhibitors and radiation and the resulting ‘immune-priming’ in NSCLC. We report our real-world experience with this novel combination in locally advanced lung cancer.

      Methods

      Between January 2016 and December 2018, consecutive patients with metastatic or progressive locally advanced NSCLC, who received immunotherapy (ICI) and also had received palliative radiation therapy were studied. Response to treatment was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Adverse events were measured using the common terminology criteria for adverse events (CTCAE) v4. Progression-free survival and overall survival were measured from the start of immunotherapy till last follow up.

      Results

      Sixty-eight patients (male – 74% and female – 26%) were available for analysis. Mean age of the population was 55% (range 34-84 years). Adenocarcinoma was the predominant histology (90%); 16 (24%) patients harbored EGFR mutations. Patients had metastatic disease (90%) at the time of starting immunotherapy - lung (75%), bone (38%), adrenal (19%) and brain (13%) were common sites involved with 55% patients having multiple metastatic sites. Thirty-seven patients (54%) had previously received radiation during the course of their disease (primary – 9, brain – 10, bone - 18); mean dose delivered was 26Gy (range 6 to 60Gy). ICI was administered as first-line in 2 patients, second-line in 39 patients and as third-line in the rest. Nivolumab was the commonest agent (96%) used; 3 patients received pembrolizumab; average cycles administered were 11 (range 1-59). Palliative RT was delivered concurrently with ICI in 28 patients (41%), of whom primary was radiated in 15 patients (22%), brain irradiation in 21% and RT to bone in 10%. Mean dose delivered was 19Gy (range 6 to 30Gy), commonest schedule used was 20Gy in 5 fractions (56%), 30Gy in 10 fractions (20%) and 6/8Gy single fraction (24%). Post RT, 43 patients (63%) developed progressive disease; 37 patients (54%) developed new lesions and 39 patients (57%) progressed at previously diseased sites, but none within the radiated field; new brain metastases were observed in 19% patients. At a median follow-up of 9.7 months, 6-month and 1-year OS were 83% and 76% respectively. The median PFS was 4.4 months (95% CI 2.8 – 6 months); 6-month and 1-year PFS were 40% and 21% respectively. Site, timing of RT and previous irradiation did not influence survival. No RT related toxicity was encountered.

      Conclusion

      We observed modest disease response with the combination of ICI and palliative hypo-fractionated RT in lung cancer. The schedule was generally well tolerated with no additional toxicity observed. A higher total dose and targeting multiple sites for radiation could improve the results and is a subject for future studies.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.