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Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.

700 Background: REG significantly improved overall survival (OS) vs placebo in patients with mCRC who progressed on available treatments in the randomized, double-blind, phase 3 trials CORRECT and CONCUR. CORRELATE aims to characterize the safety and effectiveness of REG for the treatment of mCRC in an unselected real-world patient population treated in routine clinical practice. Here we report the results of a planned IA. Methods: This global study aims to recruit 1000 patients with mCRC previously treated with approved therapies and for whom the decision to treat with REG has been made by the treating physician according to the local health authority approved label. Dose interruptions and reductions are permitted for the management of adverse events (AEs). The primary endpoint is the incidence of treatment-emergent AEs (TEAE; NCI-CTCAE v4.03). Secondary endpoints include OS, progression-free survival, and the disease control rate. The first planned interim analysis includes the first 500 patients observed for at least 3 months. Here, we report an IA of safety. Results: Median age was 65 years (range: 29–89) and 61% of patients were male. Most patients had a baseline ECOG PS 0/1 vs 2–4 (41%/43% vs 8%) and 50% had KRAS mutations. Most common metastatic sites at study entry were liver (52%) and lung (43%). The median treatment duration was 2.4 months (range: 0.1–10.6). The daily starting REG dose was 160 mg, 120 mg, and 80 mg in 53%, 34%, and 12% of patients, respectively; 26% of patients had dose reductions, 21% due to TEAEs. TEAEs of any grade occurred in 91% of patients, and in 76% TEAEs were considered REG related. Grade ≥ 3 TEAEs occurred in 55% of patients. In 31%, grade ≥ 3 TEAEs were REG related, with fatigue (7%), hand-foot skin reaction (5%), and hypertension (5%) being most common. Grade 5 TEAEs occurred in 13% of patients and were REG related in < 1%. Conclusions: In this observational study, the planned IA showed that the rate of REG-related grade ≥ 3 TEAEs appeared to be somewhat lower than rates observed in the phase 3 trials in patients with mCRC. The starting dose for approximately half the patients was less than 160 mg/day. Clinical trial information: NCT02042144.

668 Background: Ramucirumab is a human IgG1 monoclonal antibody antagonist of VEGFR-2. Overall survival (OS) and progression-free survival (PFS) in 2nd line FOLFIRI based treatment for metastatic colorectal cancer (mCRC) were improved with RAM therapy versus PBO in the RAISE trial. Recent work suggests mCRC primary tumor location is both prognostic and predictive; with improved OS and therapy-specific sensitivity observed in left (L)- vs right (R)-sided tumors. Given these findings, the RAISE trial data was subjected to post-hoc analysis to determine if sidedness influenced RAM efficacy. Methods: Primary tumor site was obtained. L-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum, while R-CRC included transverse, ascending colon and cecum. OS/PFS in L and R subgroups were analyzed via Kaplan-Meier method and unstratified log-rank test (treatments within subgroup), unstratified Cox proportional hazards model (estimate hazard ratio [HR] and 95% CI), and Wald test (treatment-by-subgroup interaction). Results: Tumor location was available for 1012/1072 (94%) patients, 699 L- and 313 R-CRC. Baseline characteristics were balanced between arms. RAM treatment enhanced L-CRC median OS by 2.5 mo (median 14.5 vs 12.0 mo) with a HR (95% CI) = 0.807 (0.675, 0.965), P = 0.019; compared to a 1.1 mo increase in median OS in R-CRC vs PBO (12.7 vs 11.6) with a HR (95% CI) = 0.971 (0.750, 1.258), P = 0.823; and, RAM enhanced L-CRC median PFS by 1.6 mo (6.0 vs 4.4 mo) and HR (95% CI) = 0.776 (0.664, 0.906), P = 0.001 compared to a 1.1 mo increase in median PFS R-CRC vs PBO (5.6 vs 4.5) with a HR (95% CI) = 0.855 (0.674, 1.084), P = 0.197. The treatment-by-subgroup interaction for both OS and PFS was not significant ( P = 0.276, 0.578, respectively). Conclusions: Despite L-CRC patients having longer OS/PFS and a seemingly stronger RAM treatment effect than R-CRC, the non-significant interaction test cannot verify sidedness as being predictive of RAM efficacy. The current study confirms ramucirumab benefits mCRC patients regardless primary tumor location. Clinical trial information: NCT01183780.

Adjuvant treatment of high-risk cutaneous melanoma (CM) patients (pts) is still an unsolved issue, since the cost-benefit ratio of high-dose IFN-α2b is under discussion. The CSF-470 therapeutic vaccine, a mini-allograft of four lethally-irradiated allogeneic CM cell lines, with BCG and rhGM-CSF as adjuvants, is currently being tested in post-surgical adjuvancy vs medium-dose IFN-2b in stage IIB-III CM pts (phase II/III trial CASVAC-0401, NCT01729663).We present here the results of the phase II part of the study. A total of 31 pts (stage IIC = 2; stage III: 29) were enrolled: 20 pts were randomized to receive CSF-470 vaccine and 11 pts to IFN-α2b. Pts assigned to the vaccine arm received i.d. 1.6×107 CSF-470 irradiated cells plus 106cfu BCG and 100μg rhGM-CSF (first day); 100 μg rhGM-CSF/day/3days were injected consecutively i.d. at the vaccination site. During the two-year treatment, pts in the vaccine arm received a total of 13 vaccinations. Pts assigned to the IFN-α2b arm received 10 MU/day/5 days a week for 4 weeks; then 5 MU 3/week for 23 months. Imaging studies were performed to follow the clinical evolution of the disease. Analysis of blood chemistry and differential white blood cell counts were performed to monitor systemic toxicity. Immune monitoring was performed at baseline and at 6, 12 and 24 months from protocol start. Also, pts were evaluated by Quality of Life Questionnaires (QOL) along the study. After including 20 pts who received a total of 176 vaccinations, we conclude that: CSF-470 vaccine was well tolerated; the main toxicity was a grade 2 reaction at the injection site; 3/20 pts presented grade 3 allergic reactions that were easily handled with anti-histamines and corticosteroids. Pts in the IFN-α2b arm presented grade 2-3 hematologic toxicity; 9 pts developed adverse events that forced treatment discontinuation provisionally or permanently. With a mean follow-up of 28 months and a maximum follow-up of 67 months, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed: 14/20 pts (70%) immunized with CSF-470 vaccine and only 4/11 pts (36.4%) in the IFN-α2b arm remain without distant metastases (p = 0.032). No significant differences in OS were yet observed. QOL was significantly superior for CSF-470 vaccine as compared to IFN-α2b treatment (p&lt;0.0002). DMF pts developed a significantly higher DTH reaction after the 7th and 12th vaccine as compared to progressing pts. These results demonstrate a clear superiority of CSF-470 vaccine plus BCG plus GM-CSF vs IFN-α2b in the adjuvant setting in pts with high-risk CM. Citation Format: José Mordoh, María Betina Pampena, Mariana Aris, Paula Blanco, Alicia I. Bravo, Juan Manuel O'Connor, Julio Kaplan, Franco Ramello, Estrella M. Levy, María M. Barrio. A randomized phase II study of the CSF-470 therapeutic vaccine plus BCG plus rhGM-CSF versus IFN-α2b in cutaneous melanoma patients stages IIB, IIC and III. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT118. doi:10.1158/1538-7445.AM2015-CT118