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Though cervical cytology, HPV DNA testing, and pre-invasive disease management has significantly reduced the number of new diagnoses of cervical cancer, women with persistent oncogenic HPV infection are at significant risk for developing invasive cervical cancer. Early stage and locally advanced disease can be cured, but women with advanced or recurrent disease have a very poor prognosis. This underscores the need for different treatment strategies for advanced cervical cancer, the most promising of which are novel therapeutics that target the ability of HPV to overcome host immune tolerance. Areas covered: This review includes new therapies being investigated for the treatment of recurrent, metastatic or refractory cervical cancer, separated into broad categories of cellular and non-cellular based strategies. Expert opinion: Advanced and recurrent cervical cancer has a poor prognosis, prompting investigations into the development of strategies that will eradicate tumor and/or overcome host immunologic tolerance of disease. It is unknown whether it will be these strategies alone or a combination of treatment modalities that will ultimately provide the best outcomes; nevertheless, the new data are promising.

5516 Background: Unlike approved IV administered therapies, Medicare is under no obligation to cover prescription medicines. We sought to evaluate the cost-effectiveness of the two FDA-approved orally administered PARP inhibitors (PARPi), olaparib and rucaparib. Methods: A Markov model was created in TreeAge Pro 2015 with nodes in the chain allowing patients to transition through response, hematological complications, non-hematological complications, progression, and death. Separately, the PARP inhibitors were compared with IV administered drugs approved for recurrent ovarian cancers including platinum-based, non-platinum, and bevacizumab-based regimens. Toxicity and mean PFS rates for the different agents were obtained from registration trial data. Costs of IV chemotherapy, managing toxicities, infusions, and supportive care were estimated using 2015 Medicare data. Incremental cost-effectiveness ratios (ICER) were calculated and survival was reported in quality adjusted life months. Results: Platinum-based combinations were the most cost-effective at $1,672/PFS mo as compared to non-platinum agents ($6,688/mo), bevacizumab-containing regimens ($12,482/mo), olaparib ($13,3731/mo), and rucaparib ($14,034/mo). Considering a cost of $114,478 for olaparib and $137,068 for rucaparib prior to progression, costs associated with PARPi were 7.1 to 8.3X more than platinum combinations. To better compare the registration trial data to PARPi data, probability was adjusted to 2nd line for rucaparib, revealing it’s ICERs’ of per month of life added to be $26,997 for bevacizumab, $17,757 for non-platinum, and $79,585 for platinums. Using the adjusted-to-2nd-line probabilities for olaparib, exhibited ICERs were $16,549 for bevacizumab, $25,637 for non-platinums and $72,083 for platinums. Conclusions: The high costs of PARPi were not balanced by costs of infusion and managing toxicities of IV drugs typically associated with lower response rates and shorter PFS in the recurrent space. Balancing incremental clinical benefit with novel therapies remains problematic and could widen disparities among those with limited access to care.

5545 Background: With the December 19, 2018 regulatory approval by the US FDA of olaparib tablets as maintenance therapy for women with deleterious or suspected deleterious germline or somatic BRCAmut advanced ovarian carcinoma, it becomes important to clarify the role of PARP inhibitors in this disease. We evaluated cost-effectiveness of olaparib in the upfront (SOLO1) versus the recurrent maintenance setting (SOLO2). Methods: Data were obtained from SOLO1, the phase 3 placebo-controlled randomized upfront maintenance study among gBRCAmut patients [median PFS greater than 49.8 vs 13.8m: HR 0.30; 95% CI, 0.23-0.41; p < 0.001, NCT01844986] and SOLO2, the phase 3 placebo-controlled randomized maintenance study among gBRCAmut patients with platinum-sensitive recurrence and at least two prior lines of therapy [median PFS 19.1 vs 5.5m: HR 0.30; 95% CI, 0.22-0.41; p < 0.0001, NCT01874353]. Investigator-assessed median PFS and toxicity data from the trials were incorporated in a Markov model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2015, the costs of pre-treatment testing (eg. gBRCAmut), medications, and management of adverse effects were analyzed. Incremental cost-effectiveness ratios (ICERs) per month of life gained and individual PFS-life year saved (PFS-LYS) were also calculated and compared. Results: In SOLO1, cost prior to progression was 1.7x that of SOLO2 ($937,440 vs $564,451). With the extended, estimated median PFS of at least 49.8m for SOLO1 and 19.1m for SOLO2, upfront maintenance therapy was more cost-effective. SOLO 1 was associated with $312,480 PF-LYS per individual patient, while SOLO2 demonstrated $498,045 PF-LYS. Maintenance olaparib was found to be more cost-effective in the 1st-line setting, with an ICER of $12,149 per month of life gained when compared directly to SOLO2. Conclusions: Although the higher cost associated with olaparib in SOLO1 reflects the longer time patients stay on drug due to extended PFS, the ICER supports early use in the disease course as first-line maintenance therapy among women with gBRCAmut advanced ovarian carcinoma.

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