Abstract 1177: Retreatment after secondary resistance: A pilot study.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Retreatment with agents to which patients have shown secondary resistance or a mixed response is usually avoided by oncologists, though recent results suggest that continuing herceptin after secondary resistance is associated with a better outcome than discontinuation. Here we present preliminary results of a pilot study in which patients were retreated with agents that had previously produced prolonged stable disease (SD), partial or complete remission (PR/CR) or a mixed response,followed by progression.This study was performed according the guidelines of the MD Anderson Cancer Center Institutional Review Board. Eleven patients with diverse, advanced cancers (median number of prior systemic therapies in the metastatic setting = four (range, 2-7) have been included to date (number of men = 8; median age = 57 years; median ECOG performance status = 1)., The median duration between the initial treatment and the retreatment regimen was 95 weeks (range 5-323 weeks). Eight of 11patients (73%) on a retreatment regimen showed stable disease (SD) >24 weeks or a partial response. Of these eight, two were retreated with precisely the same agent(s); one, with a different agent that has the same mechanism of action (EGFR inhibitor; gefitinib first and then erlotinib); and five, with the same agent(s) but with additional agents added. | N | Diagnosis | No of prior therapies | Best Prior Treatment | Gap* (weeks) | Best Retreatment | |:-- | ------------------------------------- | --------------------- | ------------------------------------------ | --------------- | ---------------- | --- | | | | | Name | Duration(weeks) | Best Response | | Name | Duration (weeks) | Best Response | | 1 | Adenocystic Carcinoma | 3 | Erlotinib | 99 | PR | 54 | Erlotinib | 69 | SD | | 2 | Hepatic Cholangiocarcinoma | 2 | Sorafenib | 7 | Mixed | 15 | Bevacizumab plus Sorafenib | 36 | SD | | 3 | Myxoid Liposarcoma | 3 | Trabectedin | 58 | SD | 92 | Trabectedin | 4 | PD | | 4 | Ewing's Sarcoma | 7 | IGF inhibitor | 148 | PR | 5 | IGF inhibitor plus mTOR inhibitor | 153+ | PR | | 5 | Rectal Adenocarcinoma | 5 | Capecitabine plus bevacizumab | 44 | SD | 95 | Capecitabine plus Bevacizumab | 24 | SD | | 6 | Ovarian Serous Carcinoma | 4 | Paclitaxel plus carboplatin | 18 | CR | 120 | Paclitaxel and Carboplatin (Bevacizumab added after 4 months) | 60+ | PR | | 7 | Colorectal Cancer | 3 | FOLFOX plus bevacizumab | 22 | CR | 26 | HAI Oxaliplatin plus HAI Irinotecan plus IV Bevacizumab | 3 | PD | | 8 | Squamous Cell Cancer of Head and Neck | 4 | Chemoradiation with Carboplatin and taxane | 7 | CR | 214 | Docetaxel plus Carboplatin plus 5FU | 6 | PR | | 9 | Colorectal Adenocarcinoma | 6 | FOLFIRI plus bevacizumab | 24 | PR | 104 | HAI Oxaliplatin and IV Bevacizumab and PO Capecitabine | 12 | SD | | 10 | Adenocystic Carcinoma | 7 | Gefitinib | 114 | SD | 322 | Erlotinib | 31+ | SD | | 11 | Invasive Ductal Carcinoma of Breast | 4 | Carboplatin plus Docetaxel plus Herceptin | 21 | CR | 383 | Carboplatin, Taxotere, Herceptin and Temsirolimus | 26 | PR | * *Gap in weeks between the previous treatment and initiation of the retreatment with some of the same drugs. Our pilot data suggest that retreatment with agents to which patients had previously shown durable SD/CR/PR or mixed response followed by secondary resistance can produce SD > = 24 weeks/ PR when given alone or in combination after a gap between initial treatment and retreatment. Plausible mechanisms accounting for this phenomenon include persistence of a suppressed clone alongside the new resistant clone, drug synergy,and epigenetic modulation during drug holidays. Further investigation of the effect of retreatment in patients with advanced metastatic disease is warranted. Citation Format: Rishi Agarwal, Aung Naing, Gerald Falchook, Jennifer Wheler, Siqing Fu, Razelle Kurzrock. Retreatment after secondary resistance: A pilot study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1177. doi:10.1158/1538-7445.AM2013-1177