Author of

• 30844

  +

  P1.04 - Immuno-oncology (ID 164)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 30935

    +

    P1.04-73 - Small Cell Transformation of Non-Small Cell Lung Cancer (NSCLC) on Immune Checkpoint Inhibitors: Case Report and Literature Review (ID 1510)

    09:45 - 18:00  |  Author(s): Paul A. Vanderlaan
    • Abstract
    • Slides

    Background
    

    Histological transformation of oncogene-driven lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with tyrosine kinase inhibitors (TKI) is a well-described phenomenon. However, it is unknown whether a similar transformation may drive acquired resistance to immune checkpoint inhibitors (ICPi) in NSCLC by altering tumor-related immune evasion.

    Method
    

    We present a case of a patient with NSCLC treated at our institution with transformation to SCLC during second line therapy with nivolumab. We conducted a review of the literature to identify similar cases and patient outcomes.

    Result
    

    This is a case of a 69 year-old woman with a 35 pack-year tobacco history presenting with stage IV squamous cell lung cancer (figure 1A). Her disease progressed within 4 weeks of first line carboplatin/gemcitabine and she was transitioned to next line nivolumab with sustained partial response lasting 18 months. She then developed rapid, bulky progression of mediastinal disease. Biopsy showed transformation to SCLC (figure 1B). Comparison of genomic profiling results from the initial NSCLC diagnosis and SCLC transformation revealed similar tumor profiles (TP53 R283fs*62). Absence of RB1 loss and initial protracted response to nivolumab suggested that transformation likely occurred as a result of treatment-induced selection pressure. The patient had a near complete response following 4 cycles of carboplatin/etoposide and remained alive 7 months post-transformation. Review of the literature revealed 7 reported cases where SCLC transformation was thought to result from acquired resistance to ICPi (Table 1).

    Conclusion
    

    We add to the emerging evidence of transformed SCLC as an acquired resistance mechanism following ICPi treatment in advanced NSCLC. Although only a few reports are available at this time, the real-world frequency may well be under-estimated due to relative infrequency of post-progression biopsies in NSCLC patients not being treated with TKIs. The underlying genomic/epigenetic mechanisms that may explain acquired resistance with neuro-endocrine transformation remain to be elucidated.

    

    Table 1. Summary of literature on NSCLC cases transformed to SCLC on ICPi

    Serial No. (Reference)	Original histology	Original genomic profile	ICPi details	Genomic profile of transformed SCLC	Outcome post SCLC transformation
    1 (Index case)	Squamous cell carcinoma	TP53 mutation	Nivolumab (2nd line, 47 cycles)	TP53 R283fs*62 mutation	Alive 7 months post SCLC
    2 (Iams et al, JTO 2018)	Adeno-carcinoma	KRAS G12C mutation	Nivolumab (2nd line, 33 cycles)	KRAS G12C mutation, TP53 R273C mutation	Died 16 months post SCLC
    3 (Iams et al, JTO 2018)	Adeno-carcinoma	KRAS G12C mutation	Nivolumab (2nd line, 36 cycles)	TP53 S315S mutation, RB1 splice site mutation	Died 11 months post SCLC
    4 (Imakita et al, Respir Med Case Rep. 2017)	Poorly differentiated carcinoma	Neg for EGFR / Alk	Nivolumab (2nd line, 3 cycles)	Not described	Died 2 months post SCLC
    5 (Abdallah et al, Lung Cancer [Auckl]. 2018)	Adeno-carcinoma	Neg for EGFR / Alk	Nivolumab (2nd line, 5 cycles)	Not described	Response after 2 chemotherapy cycles
    6 (Abdallah et al, Lung Cancer [Auckl]. 2018)	Squamous cell carcinoma	Not described	Pembrolizumab (1st line, 30 cycles)	Not described	Alive 18 months post SCLC
    7 (Bar et al, JCO 2018)	Squamous cell carcinoma	Not described	ICPi (16 months)	Not described	Poor response to chemotherapy
    8 (Bar et al, JCO 2018)	Squamous cell carcinoma	Not described	ICPi (6 months)	Not described	Poor response to 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.

• 30943

  +

  P2.04 - Immuno-oncology (ID 167)

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

  • 31013

    +

    P2.04-60 - Pembrolizumab-Based Regimens Administered at Non-Standard Frequency in Non-Small Cell Lung Cancer (NSCLC) (ID 1463)

    10:15 - 18:15  |  Author(s): Paul A. Vanderlaan
    • Abstract
    • Slides

    Background
    

    Pembrolizumab (P) administered every 3 weeks ± chemotherapy is a standard treatment option for advanced NSCLC. However, other than modeling and simulation-based analysis, there have been no post-approval studies to determine the optimal administration frequency or if longer intervals between administrations are effective.

    Method
    

    We retrospectively reviewed medical charts of 81 patients with advanced NSCLC treated with P for at least 4 cycles at a single academic center (02/2016-3/2019). 2 patients groups were selected: those who received 3 or more P-based regimens at non-standard frequency intervals between cycles longer than 3 weeks ± 3 days (group A), or those who received P-based regimens at standard frequency or up to 2 non-standard cycles (group B). Descriptive tables of demographic details, tumor characteristics, treatment details, and immune-related adverse events (irAEs) were generated. Kaplan-Meier survival analysis and Cox proportional hazards model for multivariable regression analysis were utilized.

    Result
    

    Of 81 P-treated patients, 47 (58%) had received at least 4 cycles (group A: 14, B: 33). There were no significant differences between groups in sex, stage at diagnosis, smoking status, driver oncogene mutations, PD-L1 expression, tumor mutation burden, line of therapy, performance status or grade 3 irAEs. Patients in group B were more likely to receive P + chemotherapy (group A: 0%, B: 33.3%, p = 0.02). Patients in group A were more likely to have any grade irAEs (groups A: 78.6%, B: 33.3%, p = 0.024). The reasons for any non-standard cycles in group A were: irAEs (14.3% patients), non-irAE medical issues (35.7% patients) and solely non-medical patient-physician preference (50% patients). Median time to treatment discontinuation (TTD) was significantly longer in group A than group B (24 months vs 5 months, p <0.0001), as was median overall survival (OS) (Not reached vs 14 months, p=0.0029). Patients in group A continued to show significantly longer overall survival when adjusted for confounding variables (Hazard Ratio 5.6, p=0.029).

    Conclusion
    

    Our data, though limited by sample size and single institution design, shows that a significant proportion of patients receive P at extended intervals in routine clinical practice and with no worse outcomes than would be expected for those with advanced NSCLC receiving P at label-specified 3-week intervals. Given the durability of benefit seen in such patients, this requires confirmation in larger datasets and prospective trials so as to maximize patient experience and clinical outcomes while minimizing financial toxicity.

    	Group A (≥ 3 Non-standard cycles)	Group B (Standard or ≤ 2 non-standard cycles)	p-value (chi-square log-rank test)
    	N = 14	N = 33
    Median OS, months (95% CI)	Not reached (14 - not reached)	14 (8 - not reached)	0.0029
    Median TTD, months (95% CI)	24 (17 - not reached)	5 (4-6)	<0.0001

    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.