Search

Background The optimal treatment and molecular landscape of recurrent clear cell carcinoma of the vulva (VCCC) are unknown. No reported data exist regarding the efficacy of anti-programmed death 1 (PD-1) immune checkpoint inhibition in VCCC. We report on a patient with chemotherapy-refractory recurrent VCCC, who was found to have high tumor programmed death-ligand 1 (PD-L1) combined positive score (CPS), and subsequently experienced a durable partial response (PR), after treatment with off-label fifth-line pembrolizumab. Case presentation A forty-year-old Filipino woman presented to our center with recurrent VCCC that had progressed on multiple prior lines of cytotoxic chemotherapy. She had a large 25 cm fungating left groin tumor causing marked lower limb lymphedema, pain and limited mobility. PD-L1 CPS by immunohistochemistry was 45. She was treated with off-label pembrolizumab monotherapy and had a dramatic clinical, biochemical and radiological partial response. The progression-free survival of this patient's VCCC after treatment with pembrolizumab, defined as the time from initiation of pembrolizumab until disease progression (by Response Evaluation Criteria in Solid Tumors (version 1.1)), was 8 months. While receiving pembrolizumab, she was diagnosed with concurrent secondary myelodysplastic syndrome with excess blasts (MDS-EB), thought to be related to her prior exposure to multiple lines of cytotoxic chemotherapy. This eventually progressed to acute myeloid leukemia (AML), leading to her demise. Overall survival from time of initiation of pembrolizumab till death was 16 months. Conclusion Pembrolizumab was active in this patient with chemotherapy-refractory VCCC which harbored high PD-L1 CPS. Further studies to determine the role of immune check-point blockade in the treatment of VCCC are warranted.

Objective ‘Sensible on Strength’ (SoS), a local public health initiative, is aimed at reducing high-strength beer and cider availability. The objective of this study was to assess its impact on local hospital admissions with alcohol-related liver disease (ALD) and on drinking behaviour. Design This was a retrospective cohort study in patients admitted with decompensated ALD, 3 years before and 3 years after the introduction of the SoS initiative. Hospital records of 143 index admissions with decompensated ALD were reviewed. Outcomes measures were the severity of liver disease on admission and mortality (inpatient and long-term), and change (if any) in alcohol drinking behaviour. Results Comparing patients admitted in both phases, there were no significant differences in liver prognostic scores, liver-related complications, length of stay and inpatient/long-term mortality (p>0.05). However, the SoS initiative was associated with a 33% move away from beer and cider consumption (36.3% vs 54.0%; p=0.034), but without a significant change in units of alcohol consumed. The Model for End-stage Liver Disease (MELD) score was the only independent predictor of inpatient mortality (odds ratio 1.25; p=0.025). Conclusion Despite having no apparent impact on the clinical spectrum of local ALD admissions, it is conceivable that longer follow-up is needed to determine the true impact of this initiative.

6086 Background: Precision oncology approaches in EC patients (pts) are evolving with emerging targeted therapy. We reviewed the effect of genomic findings on treatment choice and outcome in an Asian EC cohort. Methods: Recurrent or metastatic ECs were prospectively profiled with next-generation sequencing (NGS) and relevant immunohistochemistry. Clinical data were collected to assess outcomes. Results: Between 12/2014 to 12/2019, 51 Asian EC pts of endometrioid (26/51), serous (7/51), carcinosarcoma (4/51), clear cell (4/51) and mixed (10/51) histology were enrolled. 35/51(69%) of tumors were high grade. The median age at diagnosis was 56 (range 37-77), and the median lines of treatment received was 3 (range 1-8). 45/51(88%) of pts had successful NGS profiling, 31/45(69%) using FoundationOne CDx, and 14/45 (31%) on an in-house platform. Frequent mutations (>20%) occurred in PTEN (60%), PIK3CA (49%), TP53 (46%), ARID1A (27%), CTNNB1 (24%) and KRAS (22%). There were 12/51(24%) MSI-H, 25/51(49%) MSS, and 14/51(27%) MSI-unknown tumors. The 6 mth progression free survival (PFS) rate for MSS versus MSI-H pts treated with front-line carboplatin+paclitaxel (CP) was 83% versus 50% (RR 1.67, fisher’s exact 2-sided p=0.09), with a shorter median PFS after 1st line CP for MSI-H versus MSS pts (median 5.2 mth vs. 8.3 mth, not sig). Upon progression, 29/51(57%) of pts were matched to therapy based on tumor profiles. Of these, 7/29(24%), 13/29(45%) and 9/29(31%) matched to anti-PD1/PD-L1, endocrine therapy and other targeted therapy, respectively. Among 7 MSI-H pts matched to anti-PD1/PD-L1 therapy, median PFS was 14.6 mth (95% CI 0.4-29), and objective response rate was 57%(4/7). In subsequent-line, matching to endocrine therapy (HR 4.3 95% CI 0.95-19.0, p=0.06) or other targeted therapy (HR 5.1, 95% CI 1.1-24.5, p=0.04) was associated with worse PFS compared to anti-PD1/PD-L1 therapy. Despite a short median PFS after front-line CP, median overall survival (OS) was not reached for MSI-H pts, compared to 38 mth (95% CI 30.7-46.0) for MSS and MSI-unknown pts. Conclusions: MSI-H EC pts appear to have shorter PFS to front-line CP chemotherapy compared with MSS pts, but may derive durable responses from immunotherapy in subsequent-line therapy. Early use of immunotherapy in advanced MSI-H EC pts should be considered. Further optimisation of therapy is urgently needed in advanced MSS EC.

To test the hypothesis that cytoreductive nephrectomy (CN) improves overall survival (OS) of patients with synchronous metastatic renal cell carcinoma (mRCC), who subsequently receive targeted therapies (TT). We identified 261 patients who received TT for synchronous mRCC with or without prior CN. To achieve balance in baseline characteristics between groups, we used the inverse probability of treatment weighting (IPTW) method. We conducted OS analyses, including IPTW-adjusted Kaplan–Meier curves, Cox regression models, interaction term, and landmark and sensitivity analyses. Of the 261 patients, 97 (37.2%) received CN and 164 (62.8%) did not. IPTW-adjusted analyses showed a statistically significant OS benefit for patients treated with CN (HR 0.63, 95% CI 0.46–0.83, P = 0.0015). While there was no statistically significant difference in OS at 3 months (P = 0.97), 6 months (P = 0.67), and 12 months (P = 0.11) from diagnosis, a benefit for the CN group was noted at 18 months (P = 0.005) and 24 months (P = 0.004). On interaction term analyses, the beneficial effect of CN increased with better performance status (P = 0.06), in women (P = 0.03), and in patients with thrombocytosis (P = 0.01). IPTW-adjusted analysis of our patient cohort suggests that CN improves OS of patients with synchronous mRCC treated with TT. On the whole, the survival difference appears after 12 months. Specific subgroups may particularly benefit from CN, and these subgroups warrant further investigation in prospective trials.