Cost-effectiveness of poly-(ADP-ribose) polymerase (PARP)-inhibitors for the maintenance treatment after responding to first- and second-line chemotherapy in advanced ovarian cancer.

The introduction of inhibitors of poly-(ADP-ribose) polymerase (PARP) for the treatment of women with epithelial ovarian cancers (EOC) has radically changed the treatment in maintenance setting after responding to first- and second-line chemotherapy. The aim of this paper was to assess the pharmacological costs of PARP inhibitors (olaparib, niraparib, rucaparib and veliparib) in maintenance treatment after responding to first-line chemotherapy in EOC. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival (PFS)). We have considered the pivotal phase III randomized controlled trials (RCTs). Three different populations were considered: the overall population, patients with germline BRCA mutation (gBRCA) and homologous recombination deficiency (HRD) patients non-gBRCA mutation. Three thousand four hundred and twenty patients and 1209 patients were considered in maintenance treatment after responding to first- and second-line chemotherapy in EOC, respectively. At the actual price, the treatment with PARP inhibitors is not cost-effective in maintenance treatment after responding to first-line and second-line chemotherapy in EOC. A reduction in pharmacological costs is mandatory.

Cost-effectiveness of pembrolizumab in first-line for microsatellite-instability-high or mismatch-repair-deficient metastatic colorectal cancerF.

The aim of this paper was to assess the cost-effectiveness of pembrolizumab in first-line for microsatellite-instability-high or mismatch-repair-deficient metastatic colorectal cancer. We have considered the pivotal phase III randomized controlled trial of pembrolizumab in first-line for microsatellite-instability-high mismatch-repair-deficient metastatic colorectal cancer. The last available update of each trial was considered as the original source. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival). The costs of drugs are at the Pharmacy of the Mater Salutis Hospital of Legnago (VR, Italy) and are expressed in euros (€). Three hundred and seven patients were considered in the pivotal phase III randomized controlled trial. Pembrolizumab obtained a cost per month progression-free survival gained ranged from 6471 € towards mFOLFOX (5-FU, oxaliplatin and leucovorin) plus cetuximab to 7886 € towards mFOLFOX. To sum up, combining pharmacological costs of drugs with the measure of efficacy represented by progression-free survival, at the actual prize pembrolizumab cannot be considered cost-effectiveness for first-line treatment for microsatellite-instability-high mismatch-repair-deficient metastatic colorectal cancer. A reduction in pharmacological costs is mandatory.

Brigatinib is a cost-effective treatment in first-line anaplastic lymphoma kinase mutation-positive (ALK + ) advanced non-small cell lung cancer (NSCLC) with brain metastases.

Introduction: The aim of this paper was to assess the cost-effectiveness of alectinib and brigatinib in first-line for anaplastic lymphoma kinase mutation-positive (ALK+) advanced non-small cell lung cancer (NSCLC). Pivotal phase III RCTs were considered. Four hundred and eighty-two patients were included. Both trials, which compared alectinib and brigatinib versus (vs.) crizotinib (control group), respectively, showed a gain in pharmacological costs, compared to the control group, of 194.80 € for alectinib and 648.48 € for brigatinib for an entire treatment of a single patient. Brigatinib was the less expensive, with a cost of 269.78 € for each month of PFS for both intention-to-treat (ITT) population that patients with baseline brain metastases (BBM). In conclusion, combining pharmacological costs of drugs with the measure of efficacy represented by PFS, both alectinib and brigatinib are cost-effective treatments in first-line for ALK+ NSCLC. In the BBM population brigatinib seems to be the most cost-effectiveness.

Cost-effectiveness of encorafenib plus cetuximab in BRAF V600E-mutated colorectal cancer.

Recently, the introduction of encorafenib in combination with cetuximab was considered as a practice changing in BRAFV600-mutated metastatic colorectal cancer. The aim of this paper was to assess the cost-effectiveness of encorafenib plus cetuximab in the second-line treatment of BRAFV600-mutated metastatic colorectal cancer. BEACON CRC Trail was considered. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (overall survival). Four hundred forty-one patients were included. Differences in costs between the two arms (encorafenib plus cetuximab vs FOLFIRI plus cetuximab) was 59 501 €, with a cost of 17 500 € per month of overall survival-gain. Combining pharmacological costs of drugs with the measure of efficacy represented by overall survival, at the actual prize encorafenib cannot be considered cost-effectiveness for second-line treatment of BRAFV600-mutated metastatic colorectal cancer.

The cost-effectiveness of new first-line therapies approved in advanced hepatocellular carcinoma.

The introduction of targeted agents (lenvatinib) and immune-based therapies (atezolizumab in combination with bevacizumab) for first-line advanced hepatocellular carcinoma provided new therapeutic options. The aim of this paper was to assess the cost-effectiveness of lenvatinib and the combination of atezolizumab plus bevacizumab in first-line for advanced hepatocellular carcinoma. Pivotal phase III randomized controlled trials were considered. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression free survival). One thousand four hundred and fifty five patients were included. The lowest cost for month of progression free survival-gain was associated with lenvatinib, with 139.24 € per month progression free survival-gained. Combining pharmacological costs of drugs with the measure of efficacy represented by progression free survival, lenvatinib is a cost-effective treatment in first-line for advanced hepatocellular carcinoma.

The cost-effectiveness of atezolizumab in first-line for metastatic triple negative breast cancer is heavily linked to PD-L1 level.

The present analysis was conducted to assess the pharmacological costs of atezolizumab as first-line treatment in triple negative metastatic breast cancer (mBC). Pivotal phase III randomized controlled trial (RCT) was considered. Nine hundred and two patients were included. Differences in costs between the 2 arms (atezolizumab plus nabpaclitaxel versus placebo plus nab-paclitaxel) was 17 398 €, with a cost of 7564 €per month of OS-gain in the overall population and 2485 €per month of OS-gain in PD-L1-positive (≥1) population. Combining pharmacological costs of drugs with the measure of efficacy represented by the OS, atezolizumab could be considered cost-effective in first-line treatment for triple-negative mBC only in PD-L1-positive population, but a reduction of costs is mandatory.

Dose-escalation strategy in refractory metastatic colorectal cancer: A change in terms of cost-effectiveness.

The analysis was conducted to assess the pharmacological costs of regorafenib and trifluridine/tipiracil in the treatment of refractory metastatic colorectal cancer (mCRC). Pivotal phase III randomized controlled trials (RCTs) of regorafenib and trifluridine/tipiracil in the treatment of refractory mCRC were considered. We have also considered the ReDOS trial, in order to verify if the dose-escalation strategy (practice changing for regorafenib) could influences the results. Differences in OS (expressed in months) between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital and expressed in euros (€)) needed to get one month of OS. Trifluridine/tipiracil resulted the less expensive, with 1167.50 €per month OS-gained. The ReDOS trial further reduce costs with 510.41 €per month OS-gained in favour of regorafenib with the escalation-dose strategy. Both regorafenib and trifluridine/tipiracil can be considered economically sustainable treatments for refractory mCRC, apparently with a lower cost of trifluridine/tipiracil. The adoption of a dose-escalation strategy (ReDOS trial) could reverse the situation making regorafenib more cost-effective than trifluridine/tipiracil.

The role of fentanyl in the treatment of breakthrough cancer pain: Different biotechnologies, different results and different drug costs.

The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.

Cost-effectiveness of newer regimens for the prophylaxis of chemotherapy-induced nausea and vomiting: review of the literature and real-world data.

PURPOSE OF REVIEW: To investigate the cost of netupitant and palonosetron (NEPA) in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) for cancer treatment in real life. RECENT FINDINGS: A retrospective analysis of all consecutives patients with advanced lung cancer treated in platinum-based (carboplatin or cisplatin) chemotherapy and with breast cancer treated with anthracycline and cyclophosphamide -based chemotherapy at our Medical Oncology Unit during 4 years was performed. The costs of drugs are at the Pharmacy of our Hospital (&OV0556;). SUMMARY: We evaluated 110 patients with lung cancer and 55 patients with breast cancer. Concerning lung cancer, we have obtained an advantage of 133 &OV0556; in monthly medical costs of NEPA and dexamethasone (DEX) vs. the combination of palonosetron (PALO) and DEX for each patient. Concerning breast cancer, we have obtained an advantage of 78 &OV0556; in monthly medical costs of NEPA and DEX vs. the combination of PALO and DEX for each patient. Combining the medical costs of antiemetic therapy with the measure of efficacy represented by the complete response, the combination of NEPA and DEX is cost-effective for preventing CINV in HEC and MEC cancer treatment.

The introduction of a third CDK4/6 inhibitor does not change the cost-effectiveness profile in first and subsequent-lines after progression or relapse during previous endocrine therapy in patients with hormone receptor positive (HR+)/human epidermal receptor-2 negative (HER-2) advanced or metastatic breast cancer.

The aim of this study was to assess the pharmacological costs of CDK4/6-inhibitors (palbociclib, ribociclib and abemaciclib) in hormone receptor positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer (BC). We have considered pivotal phase III randomized controlled trials (RCTs) of palbociclib, ribociclib and abemaciclib for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic BC in first-line in association with letrozole or anastrozole (scenario 1) and in subsequent-lines after progression or relapse during previous endocrine therapy (scenario 2).The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). Six phase III RCTs, including 3843 patients, were considered. In the scenario 1, abemaciclib resulted the less expensive at the full dose, with 2246 € per month of progression free survival (PFS)-gained. Overall ribociclib resulted the less expensive considering the reduction in dosage (36.1% in MONALEESA-2 trial versus (vs). 36.0% of palbociclib in PALOMA-2 trial vs. 43.4% of abemaciclib in MONARCH-3 trial). The price was the same for palbociclib and abemaciclib both at full and with dose reduction. In the scenario 2, the situation was similar to the scenario 1, but with lowest costs for ribociclib per month PFS-gained both at full dose (2070 €) and at dose reduction (1391 € and 690 € at 400 mg and 200 mg, respectively). Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, ribociclib was the less expensive in both scenarios.

FOLFIRINOX is a cost-effective combination chemotherapy in first-line for advanced pancreatic Cancer.

OBJECTIVES: The analysis was conducted to assess the effect of front-line combination chemotherapies on progression free survival (PFS). METHODS: The analysis was restricted to phase III randomized controlled trials (RCTs) in first-line therapy for advanced pancreatic cancer. The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) was applied to the above phase III RCTs. We have also calculated differences in PFS between the different arms of each trial and the pharmacological costs necessary to get the benefit in PFS, for each trial. RESULTS: Our study evaluated 11 phase III randomized controlled trials (RCTs), including 4572 patients. Combining the costs of therapy with the measure of efficacy represented by the PFS, we have obtained 74.12 € per month of PFS gained for 5-FU, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX), 90.14 per month of PFS gained for gemcitabine and oxaliplatin (GEMOX) and 4708.70 € per month of PFS gained for the combination of gemcitabine plus nab-pacliatxel against gemcitabine alone. CONCLUSIONS: Combining pharmacological costs with the measure of efficacy represented by PFS, FOLFIRINOX is a cost-effective first-line for advanced pancreatic cancer.

Anti-angiogenic agents in second-line treatment for metastatic colorectal cancer: the optimization of pharmacological costs.

PURPOSE: In western Countries, colorectal cancer (CRC) is the second most common cause of death from cancer. In particular, the introduction of active new anti-angiogenic agents for the second-line treatment of metastatic CRC (mCRC) is associated with a relevant increase of costs, and it is therefore important to make a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression-free survival (PFS). METHODS: The analysis was conducted to assess the effect of second-line therapy with anti-angiogenic agents on the PFS and was restricted to pivotal phase III randomized controlled trials (RCTs). RESULTS: The present analysis evaluated four phase III RCTs, including 3938 patients. Dividing the costs of therapy by the measure of efficacy represented by PFS, we found out that the lowest cost per month of PFS gained (4581 €) was associated with the use of FOLFIRI plus aflibercept. CONCLUSIONS: Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, aflibercept in combination with FOLFIRI is a cost-effective second-line treatment for patients with mCRC.

First-line therapies in metastatic colorectal cancer: integrating clinical benefit with the costs of drugs.

PURPOSE: In light of the relevant expenses of pharmacological interventions, it might be interesting to make a balance between the cost of the new drugs administered and the added value represented by the improvement in progression free survival (PFS) in first-line for metastatic colorectal cancer CRC (mCRC). METHODS: Phase III randomized controlled trials (RCTs) that compared at least two first-line chemotherapy regimens for mCRC patients were evaluated. Differences in PFS between the different arms were compared with the pharmacological costs (at the pharmacy of our hospital). The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) was applied to the above RCTs. RESULTS: Overall 28 phase III RCTs, including 19,958 patients, were analyzed. The FOLFOX resulted the least expensive (56 € per month of PFS gained) while the addition of irinotecan to FOLFOX (FOLFOXIRI) increased only marginally the costs (90 € per month of PFS gained). Treatments including the monoclonal antibodies showed a cost per month of PFS gained of 2823 € (FOLFIRI with cetuximab in KRAS wild-type patients and liver-only metastases), of € 15,822 (FOLFOX with panitumumab in KRAS wild type), and of 13,383 € (FOLFOX with bevacizumab). According to the ESMO-MCBS, the treatments including an EGFR-inhibitor (cetuximab or panitumumab) were associated with a score of 4, while the inclusion of bevacizumab reached a score of 3. CONCLUSIONS: Our data demonstrate a huge difference in cost per month of PFS gained in modern first-line treatments in mCRC.

The Pharmacological Costs of Second-Line Treatments for Recurrent Ovarian Cancer.

INTRODUCTION: In ovarian cancer, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrence; therefore, it might be interesting to make a balance between the cost of the drugs administered and the difference in progression-free survival (PFS) and overall survival (OS). METHODS: The present evaluation was restricted to pivotal phase 3 randomized controlled trials. We calculated the pharmacological costs necessary to get the benefit in PFS and OS. The costs of drugs are at the pharmacy of our hospital and are expressed in Euros (&OV0556;). We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale. RESULTS: Our study evaluated 3 phase 3 randomized controlled trials, including 2004 patients. The most relevant increase of costs was associated with the combination chemotherapy including trabectedin, with the highest costs for month of PFS gained (15,836 &OV0556;) and for month of OS gained (7198 &OV0556;), but it substantially differs considering the data of partially platinum-sensitive populations (platinum-free interval of 6-12 months), with 3959 &OV0556; for month of OS gained. CONCLUSIONS: The addition of trabectedin to pegylated liposomal doxorubicin for the treatment of recurrent ovarian cancer can lead to an increase of pharmacological costs. Differently, considering OS in patients with platinum-free interval of 6 to 12 months, there is a halving of pharmacological costs with the addition of trabectedin to pegylated liposomal doxorubicin. These costs are in line with the spending suggested as sustainable (thresholds of <$61,500 per life-year gained).