Virtual Library

Start Your Search

Giancarlo Pruneri



Author of

  • +

    OA14 - Update of Phase 3 Trials and the Role of HPD (ID 148)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • +

      OA14.06 - Hyperprogressive Disease in Advanced Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (Now Available) (ID 1835)

      11:30 - 13:00  |  Author(s): Giancarlo Pruneri

      • Abstract
      • Presentation
      • Slides

      Background

      Hyperprogressive disease (HPD) is a paradoxical boost in tumour growth described in a subset of cancer patients treated with immune checkpoint inhibitors (ICIs).

      Method

      We retrospectively collected data about all consecutive patients with advanced Non-Small Cell Lung Cancer (aNSCLC) treated with ICIs at our Institution between 04/2013 and 12/2018. Patients were classified according to our previously published clinical/radiological criteria for HPD (Lo Russo G, Clin Canc Res 2018). (Table). All ICIs administered for ≥1 cycle were admitted. Chi-square test was used to compare qualitative variables. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analyses were performed with Cox hazard model.

      Table HPD definition on the basis of 3 concomitant out of the five possible criteria

      HPD CLINICAL & RADIOLOGICAL CRITERIA

      Time-to-treatment failure < 2 months

      Increase of ≥ 50% in the sum of target lesions major diameters between baseline and first radiological evaluation

      Appearance of at least two new lesions in an organ already involved between baseline and first radiological evaluation

      Spread of the disease to a new organ between baseline and first radiological evaluation

      Clinical deterioration with decrease in ECOG performance status ≥ 2 during the first 2 months of treatment

      Result

      We reviewed 301 cases and 257 were evaluable for response. We identified four categories: responders (R, 57 cases, 22.2%), patients with stable disease as best response (SD, 69 cases, 26.8%), patients with progressive disease as best response (P, 78 cases, 30.4%) and patients with HPD (53 cases, 20.6%). Clinical/pathological variables were uniformly distributed among groups, except for a higher rate of patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) >1 in HPD group (p = 0.0141). After a median follow-up of 23.49 months (IQR 10.72–44.21 months), median Progression-Free Survival (mPFS) and median Overall Survival (mOS) were 14,2 vs 6,5 vs 2,3 vs 1,5 months ( p < 0.0001) and 32,5 vs 17,8 vs 7,8 vs 4,1months (p < 0.0001) in R, SD, P and HPD group, respectively. The multivariate analyses, between P and HPD groups, adjusted for ICIs line, number of metastatic sites and ECOG-PS according to PFS (HR 2.448, 95% CI 2.137-2.899, p<0.0001) and OS (HR 2.481, 95%CI 2.092-2.950, p < 0.0001) confirmed the worse outcome of HPD group.

      Conclusion

      Our updated analysis confirmed patients with HPD as a distinct category that performs significantly worse than other groups, including P patients. The incidence of HPD in our cohort is relevant. The ICIs’ detrimental effect has to be taken into account and further investigated.

      Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      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.

  • +

    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.09-05 - Clinical and Biological Characterization of Lung Enteric Adenocarcinoma (Now Available) (ID 1650)

      10:15 - 18:15  |  Author(s): Giancarlo Pruneri

      • Abstract
      • Slides

      Background

      Lung Enteric Adenocarcinoma (LEA) is a rare and poorly characterized variant of Lung Adenocarcinoma (LA), defined by an intestinal differentiation in ≥50% of tumor and ≥1 colorectal biomarker at Immunohistochemistry.

      Method

      We retrospectively identified the cases of LEA diagnosed at Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy between 01/2013 and 12/2018. Next Generation Sequencing was performed with IonTorrent (ThermoFisher Scientific, Life Technologies) by using the commercial Hot Spot Cancer Panel (HCP) on DNA derived from formalin-fixed paraffin-embedded tissues. ALK and ROS-1 status was assessed with fluorescent in situ hybridization. PD-L1 expression was determined with DAKO22C3 assay. Biological data obtained from our cases were compared with those reported in Tumor Cancer Genome Atlas (TCGA) for LA, restricting the comparison only to the genes targeted by HCP.

      Result

      We identified 38 LEA cases. Main clinical and biological characteristics of the two populations are detailed in the table.

      Variable/

      gene mutation

      INT LEA (N=38)

      TCGA LA (N=660)

      %

      %

      Gender

      Female

      34.1

      51.9

      Male

      65.9

      47.9

      Unknown

      0

      0.2

      Smoking status

      Former/current

      76.3

      78.9

      Never

      15.8

      14.1

      Unknown

      7.9

      7.0

      Disease stage

      I

      2.6

      51.6

      II

      2.6

      23.0

      III

      28.9

      16.4

      IV

      65.9

      4.7

      Unknown

      0

      4.3

      TP53

      52.6

      54.1

      KRAS

      34.2

      32.4

      STK11

      23.7

      15.8

      CDKN2A

      15.8

      3.9

      APC

      7.9

      4.8

      CTNNB1

      7.9

      3.8

      EGFR

      7.9

      15.8

      KIT

      5.3

      2.1

      PI3KCA

      5.3

      5.9

      SMAD4

      5.3

      4.1

      ATM

      2.6

      8.9

      BRAF

      2.6

      8.2

      FGFR

      2.6

      0.8

      GNAS

      2.6

      3.8

      NRAS

      2.6

      0.6

      PDGFRA

      2.6

      7.4

      RB1

      2.6

      5.8

      SMO

      2.6

      2.7

      Neither ALK nor ROS-1 rearrangements were detected in our case series. PD-L1 was negative in 23 cases, 1-49% in 9 cases, not evaluable in 6 cases. Microsatellite were stable except for 3 cases with low instability and 3 not evaluable cases.

      Conclusion

      Our series of LEA was small and differed from TCGA LA for a higher proportions of males and metastatic disease. Given these limitations, our LEA genetic profile showed some difference from that of TCGA LA. In particular, LEA showed a higher incidence of STK11, CTNNB1, FGFR, NRAS, KIT and CDKN2A mutations, and a lower incidence of ATM, BRAF, PDGFRA, RB-1 and EGFR mutations. PD-L1 expression, ALK and ROS-1 rearrangements were lower than literature data in LA. Most cases were microsatellite stable. In conclusion, further research is needed to understand the biology of LEA, which seems partially different from common LA.

      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.