Search

4561 Background: Frontline cisplatin-based chemotherapy improves survival in patients (pts) with UC, but ̃50% are cisplatin-ineligible owing to poor performance status or comorbidity. The definition of platinum ineligibility is not standardized; hence, treatment decisions are almost solely made by clinical judgment. Pembrolizumab (pembro) showed antitumor activity and manageable toxicity as frontline therapy in 370 cisplatin-ineligible pts in the single arm, phase 2 KEYNOTE-052 trial (NCT02335424). We present effects of pembro on HRQoL of pts in KEYNOTE-052 who were potentially platinum ineligible in this exploratory analysis. Methods: Eligible pts for KEYNOTE-052 were adults with no prior systemic chemotherapy for advanced/metastatic UC, ECOG PS ≤2, and measurable disease per RECIST v1.1 by blinded independent central review. Pembro 200 mg IV was administered Q3W for up to 2 y. Clinical characteristics of frail pts (platinum ineligible) were identified by extensive review of real-world treatment patterns and relevant literature. Consequently, platinum ineligibility was defined as having an ECOG PS ≥2 plus ≥1 of the following: visceral disease, creatinine clearance < 60 mL/min, or age ≥80 y. HRQoL was assessed using the EORTC QLQ-C30 and EQ-5D-3L during the first 4 cycles, then every 2 cycles for 1 year or until treatment discontinuation (whichever occurred first), and at least 30 days after treatment discontinuation. Key end points were change from baseline per the QLQ-C30 global health status (GHS)/QoL score, QLQ-C30 physical functioning subscale, and EQ-5D visual analog scale (VAS). The minimum important difference (MID) was 10 for QLQ-C30 score change (improved: ≥10; stable: –10 to 10; deteriorated: –10 or less); MID for VAS score change was 7 (improved: ≥7; stable: –7 to 7; deteriorated: –7 or less). Results: Median age for 143 pts was 75 y (range, 34-91); 129 pts (90.2%) had visceral disease; 142 (99.3%) had ECOG PS 2; 1 had ECOG PS 3 (enrolled in error). Compliance rate for HRQoL questionnaires was 93.7% at baseline. At the prespecified analysis time of week 9, 77.6% of pts had improved (n = 51) or stable (n = 60) QLQ-C30 GHS/QoL scores, 64.3% had improved (n = 35) or stable (n = 57) QLQ-C30 physical functioning scores, and 62.2% had improved (n = 56) or stable (n = 33) EQ-5D VAS scores. These scores were stable throughout the HRQoL assessment period for pts who continued pembro. Conclusions: In this exploratory analysis, pembro maintained HRQoL for pts with advanced/metastatic UC in KEYNOTE-052 who were potentially platinum-ineligible per the above criteria. Together with the efficacy and safety data from KEYNOTE-052, these data suggest that pembro monotherapy is a valuable treatment option for select pts with advanced UC who are more senior and/or deemed medically frail. Clinical trial information: NCT02335424.

// Bernhard Josef Eigl 1 , Kim Chi 1 , Dongsheng Tu 2 , Sebastien J. Hotte 3 , Eric Winquist 4 , Christopher M. Booth 5 , Christina Canil 6 , Kylea Potvin 4 , Richard Gregg 2 , Scott North 7 , Muhammad Zulfiqar 1 , Susan Ellard 8 , Joseph Dean Ruether 9 , Lyly Le 10 , A. Saranya Kakumanu 11 , Mohammad Salim 12 , Alison L. Allan 4 , Harriet Feilotter 2 , Ashley Theis 2 and Lesley Seymour 2 1 BC Cancer Agency, Vancouver, BC, Canada 2 Canadian Cancer Trials Group, Kingston, ON, Canada 3 Juravinski Cancer Centre, Hamilton, ON, Canada 4 London Health Sciences Centre, London, ON, Canada 5 Cancer Centre of Southeastern Ontario, Kingston, ON, Canada 6 Ottawa Regional Cancer Center, Ottawa, ON, Canada 7 Cross Cancer Centre, Edmonton, AB, Canada 8 BC Cancer Agency, Kelowna, BC, Canada 9 Tom Baker Cancer Centre, Calgary, AB, Canada 10 BC Cancer Agency, Surrey, BC, Canada 11 Cancer Care Manitoba, Winnipeg, MB, Canada 12 Regina Cancer Centre, Regina, SK, Canada Correspondence to: Bernhard Josef Eigl, email: Bernie.eigl@bccancer.bc.ca Keywords: prostate cancer; oncolytic viruses; chemotherapy; clinical trial Received: October 12, 2017 Accepted: January 02, 2018 Published: January 17, 2018 ABSTRACT Background: Pelareorep is an oncolytic virus with activity in many cancers including prostate. It has in vitro synergism with microtubule-targeted agents. We undertook a clinical trial evaluating pelareorep in mCRPC patients receiving docetaxel. Patients and Methods: In this randomized, open-label phase II study, patients received docetaxel 75mg/m 2 on day 1 of a 21-day cycle and prednisone 5mg twice daily, in combination with pelareorep (arm A) or alone (arm B). The primary endpoint was 12 weeks lack of disease progression rate (LPD). Results: Eighty-five pts were randomized. Median age was 69, ECOG performance status was 0/1/2 in 31%/66%/3% of patients. Bone/regional lymph node/liver metastases were present in 98%/24%/6%. The median prognostic score was slightly higher in Arm A (144 vs. 129 p= 0.005). Adverse events were as expected but more prevalent in arm A. The 12-week LPD rate was 61% and 52.4% in arms A/B (p=0.51). Median survival was 19.1 on Arm A and 21.1 months on Arm B (HR 1.83; 95% CI 0.96 to 3.52; p=0.06). No survival benefit of pelareorep was found. Conclusion: Pelareorep with docetaxel was tolerable with comparable LPD in both arms but response and survival were inferior and so this combination does not merit further study.

Introduction Intensified chemotherapy improved outcomes for men with poor-prognosis metastatic germ cell cancer (GCC) and unfavorable tumor marker decline after one cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy in the GETUG-13 trial. Herein, we report our experience to date using a similar approach. Methods Patients were identified from our electronic GCC database. Men with poor-prognosis GCC and unfavorable tumor marker decline were offered intensified chemotherapy consisting of T-BEP (three cycles) plus paclitaxel, ifosfamide, and cisplatin (TIP) (one cycle), along with prophylactic granulocyte-colony stimulating factor (G-CSF) and resection of residual masses. Cisplatin, etoposide, and ifosfamide (PEI) replaced the last cycle of T-BEP for bleomycin pulmonary concerns. Serious toxicities, progression-free survival, and overall survival were evaluated retrospectively. Results Ten patients with poor-prognosis GCC were identified from May 2012 to April 2016. Eight patients had unfavorable tumor marker decline. Six were offered and received intensified chemotherapy (two T-BEPx3 + TIP and four T-BEPx2 + PEI + TIP). Serious toxicities included neutropenic sepsis, deep venous thrombosis, and C. difficile colitis, but there were no toxic deaths. One patient died of synchronous metastatic adenocarcinoma ex teratoma. The remaining five patients achieved marker-negative partial response, two had residual mature teratoma excised, and four have no evidence of disease after surgery. All are alive at a median of 63.5 months (range 46.3-65.6); one patient has grade 2 peripheral sensory neuropathy, and one patient has grade 2 cognitive disturbance. Of four patients treated with standard BEP, two have died of disease and two are alive at 51.4 and 53.6 months. Conclusions Our experience with intensified chemotherapy for men with poor-prognosis GCC and unfavorable tumor marker decline confirms that it is feasible, reasonably safe, and appears to provide results similar to those reported in GETUG-13.

In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting MET inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor of MET, RON, AXL, TIE-2, and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Patients with centrally reviewed primary TNBC and 0–1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single-arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. In stage 2, correlative studies of MET, PTEN, EGFR, and p53 on archival and fresh tumor specimens were performed along with enumeration of CTCs. 45 patients were enrolled with 37 patients having response evaluable and centrally confirmed primary TNBC (cTNBC). There were 2 partial responses (ITT 4.7 % response evaluable cTNBC 5.4 %) with a median duration of 4.4 months (range 3.7–5 m) and 15 patients had stable disease (ITT 33 %, response evaluable cTNBC 40.5 %) with a median duration of 5.4 months (range 2.3–9.7 m). The most common toxicities (all grades/grade 3) were nausea (64/4 %), fatigue (60/4 %), hypertension (58/49 %), and diarrhea (40/7 %). Six serious adverse events were considered possibly related to foretinib and 4 patients went off study due to adverse events. There was no correlation between MET positivity and response nor between response and PTEN, EGFR, p53, or MET expression in CTCs. Although CCTG IND 197 did not meet its primary endpoint, the observation of a clinical benefit rate of 46 % in this cTNBC population suggests that foretinib may have clinical activity as a single, non-cytotoxic agent in TNBC (ClinicalTrials.gov number, NCT01147484).

336 Background: Some men with mGCTs progressing after response to initial cisplatin-based combination chemotherapy are cured with CDCT as 1st salvage, however, many are not. Prognosis has recently been better defined by the IPFSG prognostic factors. HDCT with autologous stem cell rescue has been routinely offered after CR/PRm- remission with CDCT at our institution over the past two decades. We retrospectively reviewed our data to assess the validity of the IPFSG prognostic factors and evaluate the potential value of this approach. Methods: Eligible men with mGCTs progressing after at least 3 cycles of cisplatin-based chemotherapy received after 01 Jan 1990 and treated with cisplatin-based CDCT+/−HDCT (etoposide + carboplatin) were identified and data collected. Pts were classified into risk groups using IPFSG factors, PFS and OS were analyzed and results for CDCT+/−HDCT compared. Results: 38 eligible 1st salvage pts had received a median of 4 cycles (range, 1–7) of CDCT. 20 pts received CDCT alone & 18 pts received CDCT+HDCT. Overall median PFS was 24.6 months (95%CI, 7.3–28.7) and overall median OS was 34.6 months (95%CI, 17.2–51.3). Distribution by IPFSG category, 2-year PFS and 3-year OS rates within each risk category were very similar to IPFSG results. Two toxic deaths occurred with CDCT. Pts treated with CDCT+HDCT more often had better responses to 1st-line chemotherapy and pure seminoma histology. Overall pts treated with CDCT+HDCT had improved PFS (HR: 0.18; 95%CI, 0.07–0.51; p=0.001) and OS (HR: 0.25; 95%CI, 0.10–0.65; p=0.004) compared to CDCT alone. Examination by IPFSG risk category showed that the 2-year PFS and 3-year OS rates for CDCT+HDCT was higher in all prognostic groups except for the very high risk which did not have any HDCT pts. Conclusions: The IPFSG prognostic factors were valid in our 1st salvage mGCT pts. The safety of HDCT with etoposide and carboplatin was confirmed. HDCT was associated with improved PFS and OS outcomes, consistent with observations of Lorch et al (JCO 2011). Ideally the value of optimal CDCT+HDCT should be determined in comparison to optimal CDCT as first salvage therapy in men with metastatic GCT in a randomized trial.

1036 Background: Met, a receptor tyrosine kinase, is preferentially expressed in basal-like compared to luminal breast cancer. In murine models, overexpression of the oncogenic Met receptor transgene induces tumors with human basal gene expression characteristics supporting Met inhibition as a treatment strategy for triple negative (TN) breast cancer. Foretinib is an oral multi-kinase inhibitor of Met, RON, AXL, TIE-2 and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Methods: Patients (pts) with TN breast cancer and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. Tumor samples were centrally reviewed to confirm ER/PR/HER2 status and for correlative studies including Met, PTEN and EGFR expression. Stage 1 accrual required 23 response-evaluable Met unselected patients with accrual continuing if >/= 1 response or < 17 early progressions (PD