Upper GI, non colorectal: ORAL ABSTRACTS

Post by Manish A. Shah, MD:

Greetings from the Upper GI Oral Session. Today, very important practice changing abstracts were presented. You have to check these out!!

1. Gastric/ GEJ adenocarcinoma – Herceptin has activity with chemotherapy in Her-2 positive gastric/ GEJ adenocarcinoma! Van Cutsem (LBA4509). This was the first demonstration of the benefit of biologic therapy in this disease. Patients receiving chemotherapy alone (cisplatin/capecitabine) had a median survival 11.1 months, whereas patients receiving the same chemotherapy + herceptin had a median survival of 13.8 months (HR 0.74, 95%CI 0.60 – 0.91), p = 0.0046.

2. Biliary Tract tumors – Patients with biliary tract tumors have superior survival with gemcitabine and cisplatin versus gemcitabine alone, 8.3 mo vs 11.7 mo HR 0.7, 95%CI 0.54-0.89 (Valle abs 4503). 50% of patients enrolled were cancers of the biliary tree, 30% cancers of the gallbladder. Gemcitabine/Cisplatin is now a standard of care option for this group of tumors.

3. The other notable study was ESPAC-3 (Neoptolemos LBA4505), which examined FU/LV (Mayo clinic schedule) versus gemcitabine in the adjuvant setting for resected pancreas cancer. This showed absolutely no difference in survival, essentially supporting the efficacy of FU in this disease (or the lack of efficacy of gemcitabine!). Their next study (ESPAC-4) is to examine gemcitabine versus gemcitabine/capecitabine in the adjuvant setting for resected pancreas cancer.

There were notable disappointing studies as well:
i. Ajani (abs 4511) examined in a 1053 patient random assignment study cisplatin/S1 versus cisplatin/ FU in metastatic gastric/ GEJ adenocarcinoma. This was negative for superiority – Cis/S1 is equal to Cis/FU.
ii. Colucci (abs 4504) examined 400 patients in a random assignment study examining gemcitabine versus gem/cisplatin in pancreas cancer. Pancreas cancer remains a challenge! (or an opportunity…)

Also notable was Dr. Ilson keeping presenter’s honest! Arnold (abs 4508) showed that octreotide significantly increased the time to progression for mid-gut neuroendocrine tumors. The most significant finding is that octreotide is effective whether these tumors are functional or not. However, as Dr. Ilson questioned, what is the benefit of early octreotide if there is no difference in survival? Reiss (LBA4506) showed that prophylactic enoxaparin can reduce the incidence of symptomatic thromboembolism without significantly increasing the risk of bleeding in metastatic pancreas cancer. However, as Dr. Ilson asked, what is the benefit of reducing the risk of VTE if these patients would have just gotten treatment at the time they developed the VTE? The cost may be substantial.

‘Til next time. That’s all folks.

Gastrointestinal, non CRC – Posters and Poster Discussion

Post by Manish A. Shah, MD:

Greetings from ASCO, Sunday May 31 – GI, non-colorectal General Posters and Poster Discussion. Today was a big day for upper GI abstracts. Drug development is alive and well in this diverse and heterogenous group of tumors. Below are some highlights:

Biliary Tract tumors – I believe one important study was presented by Dwary (abs4521) in which, for the first time, it was demonstrated that gemcitabine/platinum therapy was significantly better than best supportive care (or 5-FU) in biliary tract cancers. Gem/platinum (either cis or oxali-) was the backbone combination of several studies examining chemotherapy with anti-EGFR therapy (i.e. Malta abs4520, Gruenberger abs4586, Furuse abs4579, and Zhu abs4578). Finally, some data on drug eluting beads was also presented, (Lencioni abs 4523, Dhanasekaran abs 4524) which were provocative but requires validation.

Hepatocellular Cancer – Studies looked at anti-angiogenic therapy, including bevacizumab + erlotinib (Hsu abs 4585), which looked very promising and there was very preliminary data of its activity in the 2nd line setting (Kaseb abs 4522). Toh (abs 4581) examined ABT-869 (a novel oral selective inhibitor of VEGF and platelet derived growth factor) and Raoul (abs 4577) examined brivinib (a novel orall VEGF and FGF inhibitor) in HCC, both with provocative phase II results.

Pancreatic Cancer – Of significant interest, and perhaps a hint of things to come, include two studies of novel formulations of paclitaxel with gemcitabine in pancreas cancer. Von Hoff (abs 4525) demonstrated data on the prognostic significance of SPARC (Secreted Protein Acid Rich in Cystein) which is overexpressed in the tumor and surrounding stroma and is associated with poor clinical outcomes. The novel formulation of paclitaxel, nab-P (nanoparticle albumen bound paclitaxel), improves the delivery of paclitaxel to the tumor by the albumen binding SPARC. The other study examined the formulation EndoTAG-1, a cationic liposomal formulation of paclitaxel, that attacts endothelial cells of tumor blood vessels (Loehr abs 4526). Both studies provided sufficiently interesting signals to support the initiation of large phase III studies in pancreatic cancer.

Gastric/ Esophagus – Vashist (abs 4519) presented interesting data on the prognostic significance of bone marrow micrometastasis in esophageal cancer. The difficulty with the data, however, was the not insignificant rate of false positives (i.e. those with bone marrow micrometastasis who had prolonged survival). Kelsen (abs 4512) presented data on a modified schedule of administration of docetaxel, cisplatin, and fluorouracil in combination with bevacizumab in gastric/ GEJ cancer. With a median survival of 16.3 months, these data suggest a role of antiangiogenic therapy in upper GI cancers that are currently being validated in phase III evaluation. Preoperative bevacizumab with chemotherapy and radiation is tolerable, and importantly without an increase in surgical complications, with accrual ongoing (Ilson abs 4573).

More to follow tomorrow, including the results of the TOGA study – A randomized phase II study of trastuzumab in Her-2 positive gastric cancer. Sleep tight!

Gastrointestinal, Non-colorectal

Post by Manish A. Shah, MD:

Greetings from ASCO. Here is a brief update of the GI, non colorectal presentations:

Shroff, R.T. et al. (abs 4500) – The IGFR pathway is implicated in promoting oncogenic transformation, growth and survival of several malignancies, including pancreatic cancer. The investigators identified an association of 3 SNPs (IGF1R IVS20431A>G, IRS1 G971R, and IGF2*4325A>G) with patient survival, independent of other known prognostic factors. However, the function of these SNPs in the IGFR pathway remains unclear.

Kindler, H.L, et al. (abs 4501) – The TRAIL death receptor family is an attractive target in pancreas cancer. The study reported on 13 patients treated with 2 doses of AMG655 (an agonist of DR5, death receptor 5), with 2/13 patients with prolonged progression free survival. This is very preliminary data, and we await the results of the already completed a randomized phase II study evaluating AMG655 in pancreas cancer.

Jhawer, M et al (abs 4502) – This was a preliminary phase II report of foretinib (an oral dual cMET/VEGFR2) multi-kinase inhibitor in gastric/GEJ adenocarcinoma. The investigators found that cMET is less frequently amplified in gastric cancer in the US than previously believed, and as a result the study showed no patients with tumor response and short durations of stable disease. Investigators are attempting to better understand the pathway to better develop this class of drugs.