Epidermal growth factor receptor (EGFR) inhibitor–related skin toxicity: Review of interim data from a phase II study (20060314) of panitumumab (pmab) with FOLFIRI in the first-line treatment of metastatic colorectal cancer (mCRC)

e20634 Background: Skin toxicity that can impact quality of life as well as treatment adherence is commonly associated with EGFR therapy. Despite their particular importance in terms of making decisions regarding supportive care, time to onset and maximum grade of skin toxicity are seldom reported. Pmab is a fully human monoclonal antibody directed against the EGFR with demonstrated monotherapy activity in patients (pts) with wild-type KRAS expressing, chemotherapy refractory, mCRC. Methods: In this single-arm study, first-line pts with histologically confirmed mCRC were enrolled to receive pmab (6mg/kg) and FOLFIRI every 2 weeks. This trial is ongoing to evaluate the primary endpoint of objective response rate and secondary endpoints including disease control rate, duration of response, time to response, progression-free survival, time to progression and other safety aspects. The focus of this abstract is skin toxicity. Results: Cutoff for the initial interim analysis was 27 June 2008. Of the 154 pts enrolled, 68% are male; median age is 64 years (range 21–84) and 95% of pts had ECOG PS 0–1. A total of 97% of pts had experienced at least one adverse event (any grade) and 55% of pts had experienced a grade 3/4 event. Grade 3/4 skin and subcutaneous toxicities were observed in 20% of pts ( Table ). Median time to first cutaneous toxicity and median time to most severe toxicity were 9 (95%CI, 7–13) and 14 (95%CI, 13–16) days, respectively. The most severe toxicity was grade 4 in one pt. Conclusions: Combining pmab with FOLFIRI in the first-line setting is a well-tolerated regimen. Skin toxicity was observed in 92% of patients; onset, incidence, and severity of which appears to be comparable to published data. Management of skin toxicities will be presented. [Table: see text] [Table: see text] </jats:p

33. Commission de la Statistique Stellaire

In the wide field of research covered by the Commission considerable progress has been made in recent years, and it is only possible here to touch briefly on the results of a few lines of investigation, without any attempt to completeness.Stellar luminosities. On the basis of the new list of Mount Wilson spectroscopic parallaxes and a compilation of the long series of modern trigonometric parallaxes A. van Maanen finds 617 objects within a distance of 20 parsecs from the sun. It is very doubtful, however, if we know all the stars even in the region of 5 parsecs radius. Almost all the known stars within 20 parsecs belong to the main sequence, the faintest star being of absolute magnitude +16.6. The most interesting deviations from the main sequence are the three “white dwarfs”, Сотр. of Sirius, Comp. o2 Eridani, and van Maanen’s F type star. G. P. Kuiper lists 3 additional white dwarfs at larger distances which were estimated to be of types Bo, B7 and A2. For the first two stars, A.C. 70°8247 and Wolf 1346, a revision of the spectral types by Adams and Humason gives A2 and A5, respectively, although the spectra differ considerably from normal ones. The A2 star in Kuiper’s list is the one discovered by Oosterhoff in the region of the cluster h, X Persei; its spectral characteristics have been examined by Öhman and by Humason. The absence of the high-numbered members of the Bahner series and of the continuous absorption at the Balmer limit seems to be an important criterion of such stars. A white dwarf of quite peculiar spectrum (type probably about B8) is the companion of o Ceti discovered spectro-graphically by Joy in 1922. There appear several additional deviations towards faint magnitudes from the main sequence which may be classed more or less safely among the white dwarfs. A few such cases have been discussed at Lund by J. Tuominen.</jats:p

Updated analysis of a phase II study (20060314) of panitumumab (pmab) with FOLFIRI as first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)

4085 Background: The fully human anti-epidermal growth factor receptor monoclonal antibody pmab, has proven monotherapy activity in chemotherapy refractory mCRC pts with wild-type KRAS-expressing tumors. This first-line, single-arm phase II study is prospectively evaluating whether KRAS status predicts response to treatment when pmab is combined with FOLFIRI. Methods: In this ongoing study, pts with histologically confirmed mCRC (no prior systemic treatment) and ECOG PS 0–2 were enrolled at 36 sites across Europe. Pmab (6mg/kg) and FOLFIRI are administered every 2 weeks. The primary endpoint is objective response rate; secondary endpoints include disease control rate, duration of response, time to response, progression-free survival, time to progression and safety. Results: Data cut-off for the initial interim analysis was 27 June 08 and pending approval of protocol amendment 2, the cut off date for 16 week response rate is 15 Oct 08. Of the 154 pts enrolled, 68% are male; median age is 64 yrs (range, 21–84) and the majority (95%) of pts had ECOG PS 0–1. All pts have received at least one cycle of study treatment; 18% of pts have received ≤2 cycles of full combination therapy and the median number of cycles received is 6. At time of data cut-off, 112 patients (73%) were still receiving at least one element of combination therapy and 29% had stopped treatment with pmab. The most common reason for discontinuing treatment was disease progression (10%). Median follow-up time was 14.3 weeks for all enrolled pts. A total of 97% of patients had experienced at least one adverse event (any grade) and 55% of patients had experienced a grade 3/4 adverse event. There were four reported grade 5 events (hematemesis, rectal hemorrhage, vena cava thrombosis, general physical health deterioration). At time of interim analysis, tissue samples for KRAS analysis are available for approximately 80% of patients. Conclusions: Combining pmab with FOLFIRI in the first-line setting appears to be a well-tolerated regimen. Response rate at 16 weeks in the overall population and by KRAS status and updated safety will be presented. [Table: see text] </jats:p

Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: Final results of a GERCOR phase II trial (ERaFOX).

8 Background: Chemoradiotherapy (CRT) for locally advanced cardia and esophageal cancer is based on 5-FU combined with cisplatin, which could be favorably replaced by oxaliplatin (Ox). Cetuximab (C) has demonstrated synergism with both radiotherapy (RT) and platinum-based chemotherapy. ERaFOX trial was evaluating the safety and efficacy of the addition of C to CRT with FOLFOX. Methods: Main inclusion criteria were: stage III squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction; WHO PS 0-1; age 18-80 years; weight loss &lt;15% in the last 6 months. Patients (pts) received 2 cycles of FOLFOX induction therapy (Ox 85 mg/m2/d1, folinic acid 400 mg/m2/d1, 5-FU 2,400 mg/m2/d1-2, q2w) plus C (first infusion 400 mg/m2 then 250 mg/m2, q1w), then RT 50.4 Gy (1.8Gy/d x 28 fractions) with FOLFOX plus C (same doses, except 5-FU 1,800mg/m2/d1-2). Tumor evaluation was performed at the end of CRT (RECIST and endoscopic ultrasonography). The primary endpoint was overall response rate (ORR), with a 50% threshold for efficacy (Simon Minimax two-stage design). Results: From Nov 2007 to Feb 2010, 80 pts were enrolled in 12 centers. The characteristics of the 79 eligible pts were (1 ineligible pt for stage IV disease): male/female 60/19, median age 63 (23-79), PS 0/1/ND 47/31/1, squamous/adenocarcinoma/undifferentiated 53/25/1; esophagus/cardia 74/5; median daily caloric intake 1,720 Kcal (550-3160). 74 pts were treated by CRT (5 pts experienced anaphylaxis during the first cetuximab infusion). ORR (ITT) was achieved in 61 pts (77.2%), 6 pts (7.6%) had stable disease, and 9 pts (11.4%) had disease progression (3 pts were not evaluable). Grade 3-4 toxicities induction therapy/CRT were (%): neutropenia: 7.6/28.4; febrile neutropenia: 0.0/2.7; vomiting: 1.3/4.0; mucositis: 1.3/5.4; diarrhea: 3.8/2.7; dysphagia-esophagitis: 1.3/13.5; rash: 7.6/10.8; allergy 8.9/0.0. One toxic death (1.3%) occurred after CRT related to esophagitis with GI bleeding. Conclusions: Threshold for efficacy was reached with an ORR of 77.2%. Chemoradiotherapy with FOLFOX plus cetuximab is active and has an acceptable toxicity profile in patients with locally advanced cardia or esophageal cancer. No significant financial relationships to disclose. </jats:p

28. Commission des Nébuleuses et des Amas Stellaires

During the past three years observational and theoretical work has been uncommonly extensive and fruitful in two of the fields within the interests of Commission 28—namely, the distribution of external galaxies and the analysis of diffuse nebulosity, the latter including interstellar absorbing material. Important work is also under way at a number of observatories in the interpretation of planetary nebulae. Studies of clusters, however, have been limited to a few active workers, and progress has not been rapid in the analysis of individual galaxies.</jats:p

33. Commission de la Statistique Stellaire

The following report, which has been drawn up partly on the basis of the reports of the members of the Commission, touches briefly and without any attempt at completeness a few points of the recent developments in certain important fields falling within the domain of the Commission.</jats:p