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R. Prenzel



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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-013 - Incidence of EGFR, KRAS, BRAF, ALK, and P53 alterations in a cohort of 159 consecutively tested patients from a certified lung cancer center, correlation with clinical characteristics and treatment outcome. (ID 2613)

      09:30 - 09:30  |  Author(s): R. Prenzel

      • Abstract

      Background
      The incidence of EGFR mutations has been systematically analyzed in a large cohort in Germany within the REASON trial. However, systematic data on KRAS, BRAF, ALK, and p53 within the same cohort have not been published in German cohorts of patients with lung cancer. Therefore we studied the incidence of these alterations in 159 patients from a single center and correlated these with clinical characteristics and survival.

      Methods
      159 patients from a single center diagnosed with lung cancer were studied for the presence of EGFR mutations, ALK rearrangements, KRAS codon 12/13/61 and BRAF V600E and G469A, as well as inactivating p53 mutations. Methods for the detection of EGFR mutations included Sanger Sequencing and hybridization based COBAS testing. ALK rearrangements were either tested by RT-PCR or ALK-FISH (break apart probe, Vysis). BRAF mutations were detected by allele specific PCR, KRAS and p53 by Sanger Sequencing

      Results
      159 consecutive patients at the lung cancer center of the Pius-Hospital Oldenburg were studied. In all cases EGFR mutations status was successfully determined. 33/159 (21%) had EGFR mutations, of which 3 had primary resistance mutations. 5/132 successfully studied pts had ALK rearrangements (3,7%). 29/142 (20%) successfully studied for KRAS mutations had codon 12 or 13 mutations. 2/136 (1,4%) successfully studied for BRAF mutations had G469A (2) mutations, V600E mutations were not observed. p53 mutations were observed in 47% of successfully studied pts (21/45 pts). Just analyzing the 60 never or light smokers (< 100 cigarettes lifelong or < 10 packyears and ex-smoker), revealed 23/60 (38%) EGFR mutations, 4/44 (9%) ALK rearrangements, 4/49 (8%) KRAS mutations, 1/49 (2%) BRAF mutations and 7/19 (37%) p53 mutations, demonstrating that EGFR and ALK were overrepresented in never-light smokers, whereas BRAF, KRAS and p53 mutations were overrepresented in smokers. ALK, EGFR, KRAS and BRAF mutations were mutually exclusive in this patient population. However p53 mutations were observed in pts with activating EGFR mutations in 7/15 successfully studied cases. Outcome in the different subgroups will be presented at the meeting.

      Conclusion
      EGFR and ALK mutations were overrepresented in never-light smokers, BRAF and KRAS mutations were underrepresented. P53 mutations occurred independently of smoking status in combination with EGFR mutations, but not ALK- translocations. OS data will be presented at the meeting.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P3.10-028 - Pathologic complete remission after induction chemotherapy and intercalated Erlotinib in EGFR-mutated adenocarcinoma stage IIIA: Case report. (ID 1784)

      09:30 - 09:30  |  Author(s): R. Prenzel

      • Abstract

      Background
      EGFR TKI treatment is standard of care in patients with metastasized NSCLC carrying an activating EGFR mutation. However, induction concepts in locally advanced NSCLC with EGFR mutation including TKI have not been studied extensively. Recently new focus has been shed on intercalated regimens of chemotherapy and TKI, showing improved PFS as well as OS. This concept was used as induction regimen in a female patient with activating EGFR mutation as well as p53 mutation and stage IIIA 3 multilevel.

      Methods
      Patient was diagnosed and worked up according to standard imaging, histology and immunohistology methods. EGFR, KRAS, BRAF, ALK and P53 mutation analysis was performed as described by Halbfass et al. Remission induction was measured by RECIST 1.1, regression grading by Junker criteria.

      Results
      A female caucasian 62 y.o. never smoker was diagnosed with TTF1+ adenocarcinoma G3 of the upper lobe of the lung, c2T3 (extension to mediastinal pleura) c2N2 (LN 2R and 4R) c2M0, UICC7 IIIA4 (Robinson). Molecular analysis after microdissection revealed WT for ALK, KRAS and BRAF, but an activating EGFR mutation Exon19 (p.Leu747_Ala750delinsPro), as well as a TP53 mutation in exon 8 (p.Val272Met (c.814G>A) (Sanger Sequencing). Induction therapy was started with erlotinib 150 mg/die p.o. days -12 to -2 in order to prove responsiveness of the tumour to TKI. On day 0 partial response was achieved. Therapy was continued with 3 cycles of Docetaxel 75 mg/m2 d1 and Cisplatin 50 mg/m2 d 1 and 2 qd22 with intercalated Erlotinib 150 mg/die p.o on days 4-19. Almost complete radiologic remission was achieved after 2 cycles The patient underwent R0 resection (upper lobe resection and radical lymphadenectomy) 4 weeks after day 1 of the 3[rd] cycle of chemotherapy, pathologic examination revealed T0N0 (mic+) with only one insula of tumor cells in an N2 lymph node, demonstrating regression grade III in the primary tumor and Grade IIB in the lymph nodes, according to the Junker classification. Molecular analysis of residual tumor cell insula revealed the same EGFR and p53 mutations as the primary tumour. The patient underwent postoperative radiotherapy of the mediastinum. No additional therapy, including TKI was administered postoperatively.

      Conclusion
      Intercalated TKI treatment might be a promising treatment choice in patients with EGFR mutated locally advanced NSCLC. A phase II trial is currently being planned to expand knowledge in this challenging field.

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      P3.10-029 - Second line chemotherapy exposure in a German Cancer Society certified lung cancer center: single center experience of 3 years and relevance for maintenance therapy (ID 2623)

      09:30 - 09:30  |  Author(s): R. Prenzel

      • Abstract

      Background
      One of the strongest rationale for maintenance therapy in NSCLC is the fact that exposure to 2nd line therapy is only 40-60% in clinical trials in specialized treatment centers. Even with follow-up intervals of 6 weeks, the 2nd line treatment rate does not seem to increase in clinical trials. One of the main arguments for maintenance treatment not widely adopted in Germany is that 2nd line exposure in international clinical trials does not reflect the situation of treatment management in Germany. Therefore, we analyzed the exposure of patients with stage IV NSCLC in one German Cancer Society certified Lung Cancer Center since certification, as long term follow-up data are available.

      Methods
      All primary lung cancer cases stage IV in the lung cancer center were analyzed based on the documentation files between 2009 and 2013. Patients were followed between 1st and 2nd line therapy every 6-8 weeks according to S3 guidelines.

      Results
      203 patients were diagnosed with NSCLC IV (UICC7), or had systemic relapse of localized disease and were treated with 1st line therapy for metastatic disease. Of these, 130 (64 %) received 1st line combination therapy with Carboplatin, 44 (22%), 21 (10%) with TKI 1st line therapy and 8 (4%) with platin-free single agent therapy. 32 (16%) of all patients received maintenance therapy, most of them with bevacizumab. Of 203 patients, 168 progressed after 1st line therapy or 1st line and maintenance therapy. 111/163 (66%) pts. received 2nd line therapy. 57 pts (34%) did not receive 2nd line chemotherapy. Reasons for not receiving 2nd line therapy were mostly associated with intercurrent bone metastases that needed surgery and or radiotherapy and CNS metastases requiring radiation, as well as non-cancer related causes. Of 23 pts receiving maintenance therapy and requiring 2nd line therapy, 20 (87%) received 2nd line therapy.

      Conclusion
      In a certified lung cancer center and stringent follow-up every 6 to 8 weeks, about 1/3 of patients do not receive 2nd line therapy. The application of maintenance therapy raised the chances of receiving 2nd line therapy. Multiple metastases, especially bone and CNS, requiring radiation therapy, were associated with not receiving 2nd line therapy. These data suggest that maintenance therapy should be considered for pts after 1st line therapy and that radiation therapy for bone and CNS metastases should if possible be accompanied by systemic treatment.