Author of

• 11946

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  P2.24 - Poster Session 2 - Supportive Care (ID 157)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Supportive Care
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11985

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    P2.24-039 - Renal failure is the first cause of double maintenance (bevacizumab + pemetrexed) discontinuation for toxicity in real world setting (ID 2491)

    09:30 - 09:30  |  Author(s): A. Toffart
    • Abstract

    Background
    Maintenance treatment, with either bevacizumab or pemetrexed, has been shown to increase PFS and overall survival. Two trials have compared double maintenance (DM) therapy (pemetrexed + bevacizumab), to single drug maintenance (bevacizumab in AVAPERL and POINTBREAK studies). Conflicting results were found. Before definitive conclusions can be driven from these studies and other ongoing study (ECOG 5508), the purpose of our retrospective study was to determine in real world setting the frequency of double maintenance discontinuation for adverse event, and to describe the main toxicities occurring during double maintenance.

    Methods
    All patients who received at least one cycle of pemetrexed and bevacizumab as maintenance treatment were identified from the Oncology Pharmacy database of participating centers since year 2011. All the charts were analyzed retrospectively to obtain clinical data. Lab results were noted for haemoglobin, creatinine and liver enzymes before starting and after receiving multiple doses of pemetrexed and bevacizumab.

    Results
    Included were 87 patients treated with two to six cycles of induction chemotherapy (median 4), combining platinum with pemetrexed and bevacizumab, followed by at least one cycle of bevacizumab and pemetrexed as maintenance treatment. All patients received supplementation of vitamin B12 and folic acid during chemotherapy. Baselines characteristics (%): male 54: stage IV 96,5; adenocarcinoma 96,5; median age 58 yr. 57,8% of patients had objective response after induction chemotherapy, and 42,2% had stable disease after induction chemotherapy. At cut off date: treatment was still ongoing for 17 patients (19,8%); 40,6% of patients stopped DM for progressive disease; 33,3% of patients stopped DM for toxicity (out of these 33% of patients, 42% went on single maintenance with Pemetrexed and 58% with Bevacizumab); 11,6% of patients stopped DM for patient/physician decision, and 14,4% for other reasons. The most common toxicity responsible for DM discontinuation was renal failure (52%).

    Reason for discontinuation (%)	POINTBREAK	AVAPERL	This study
    Progressive disease	61,0	54,7	40,6
    Adverse event	13,7	21,6	33,3
    Others reasons	19,8	23,5	25,8

    Conclusion
    This retrospective study suggests that in real world setting, double maintenance is frequently discontinued for adverse event (33,3% of patients). The most frequent adverse event was renal failure (half of the cases). Further analyses are ongoing in order to identify any predictive factors for renal failure occurrence and will be presented at meeting. These results suggest that particular caution should be taken in order to preserve renal function whenever double maintenance (pemetrexed + bevacizumab) is considered in a patient with stable or responding tumour after induction chemotherapy consisting in platinum, pemetrexed and bevacizumab.

• 12386

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12396

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    P3.02-010 - A PCR-based test detecting ectopic expressions of placenta/germline genes can predict aggressive lung tumours (ID 1648)

    09:30 - 09:30  |  Author(s): A. Toffart
    • Abstract

    Background
    Cell transformation and tumour progression are associated with severe alterations of the epigenetic control of gene expression. Although the abnormal repression of tumour suppressor genes has been thoroughly investigated, the concept of tissue-specific gene aberrant reactivations in cancer is only starting to emerge. The extent of this process has not been reported yet, mainly because of the difficulties in detecting these expressions by the currently used transcriptomic analyses

    Methods
    We have developed a simple approach, exploiting genome wide expression data, which has enabled us to demonstrate that these "off-context" gene activations occur in any cancer, providing a universal source of cancer biomarkers. By applying this analysis to our series of lung cancer patients (n=297) with the corresponding precise clinical annotations and 5 to 10 years patient follow-up, we found that hundreds of germline-specific genes are ectopically expressed in the tumours and that a subset of 26 genes are specifically activated in a subgroup of highly aggressive metastatic-prone tumours, even at an early stage of the disease. This approach has enabled us to define and isolate a homogeneous group of very aggressive tumours called P3 with at least 3 genes ectopically expressed, independently of other prognosis parameters (histo-pathological or stage) (Rousseaux et al. Sci Transl Med 2013, 5 (186): 186ra66).

    Results
    Based on these data we setup a PCR based test to directly rank lung tumours by detection of the prognosis associated gene activations. This test was first validated on a series of 60 tumour samples from the same cohort (also analyzed by an affymetrix transcriptomic approach), which revealed the remarkable robustness of the PCR approach and showed a higher sensitivity of the PCR-based detections in tumour ranking. We then extended these PCR-based analyses to include additional patients with precise clinical and pathological annotations and 10 years follow-up but for whom transcriptomic data were not available. Here again we could show that our test successfully ranked the patients into groups with significantly different survival probabilities. we show here the intermediate analysis on a first group of 88 patients without lymph node metastasis treated by surgeryFigure 1

    Conclusion
    In conclusion we are ready to launch a prospective study based on this PCR test to evaluate its ability to predict tailored follow up of patients after surgery and also tumour sensitivity to design specific targeted therapies including immunotherapy since this ectopic activation may lead to very innovative treatment .