Cost Effectiveness of the Third-Generation Tyrosine Kinase Inhibitor (TKI) Ponatinib, vs. Second-Generation TKIs or Stem Cell Transplant, as Third-Line Treatment for Chronic-Phase Chronic Myeloid Leukemia

7543 Background: Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKC and the PI3K/AKT pathway, induces tumor cell apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. Over-expression and activity of PKC and PI3K/AKT are associated with poor prognosis and treatment resistance in NSCLC. This multicenter phase II trial of enzastaurin as second- and third-line treatment of NSCLC determined the rate of progression-free survival (PFS) at 6 months (mos). Secondary objectives included safety and the rate of overall survival (OS) at 12 mos. Methods: Eligibility included metastatic (stage IV and wet IIIB) NSCLC and prior platinum-based chemotherapy. Patients (pts) received 500 mg of oral enzastaurin, once daily, until disease progression or unacceptable toxicity occurred. All pts were eligible for 2nd or 3rd line treatment. Results: In the 54 pts enrolled [54% M, 46% F; median age: 63 (range: 43–82); 22.2% stage III, 77.8% stage IV, ECOG PS=2], adenocarcinoma was the most frequent diagnosis (67%). Prior therapies included radiotherapy (74%) and EGFR inhibitors (28%). At the final analysis, the median PFS was 1.9 mos (95% CI: 1.7–1.9), and the PFS rate at 6 mos was 14% (95% CI: 4.4%–23.6%). The median OS was 9.9 mos (95% CI: 6.5–14.6). The OS rate at 12 mos was 46.3% (95% CI: 32.1%–60.5%). Nineteen pts (35%) had stable disease (SD); none had a complete or partial response. Ten (19%) pts were on-study for =6 cycles, 3 of whom continued for >10 months. The most common toxicity, fatigue (grade =2, n=15), occurred within 1 week of enrollment and was not reported in pts with SD. Grade =3 toxicities observed were ataxia (n=1), fatigue (n=2), thrombo-embolism (n=1), and anemia (n=1). Two pts discontinued due to fatigue and dizziness. Five pts died on-study and 4 within 30 days of discontinuation due to PD. Post-study chemotherapy (n=28) included bevacizumab, erlotinib, pemetrexed, gemcitabine, cisplatinum and paclitaxel. Conclusion: Although no objective tumor responses occurred, 14% of the pts were progression-free at 6 months. Based on encouraging survival and tolerability data, further evaluation of enzastaurin as a single agent or in combination, is warranted in NSCLC. No significant financial relationships to disclose.

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PCN87 The Cost Effectiveness of Cetuximab (Erbitux) in the Third Line Treatment of Metastatic Colorectal Cancer in the UK

Value in Health ◽

10.1016/j.jval.2011.08.1188 ◽

2011 ◽

Vol 14 (7) ◽

pp. A450

Author(s):

R. Perard ◽

Y. Samyshkin ◽

A.L.G. Guillermin

Keyword(s):

Colorectal Cancer ◽

Cost Effectiveness ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

The Third ◽

Third Line ◽

The Uk ◽

The Cost ◽

Third Line Treatment

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Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era

Cancers ◽

10.3390/cancers13153887 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3887

Author(s):

Valéry Refeno ◽

Michele Lamuraglia ◽

Safae Terrisse ◽

Clément Bonnet ◽

Clément Dumont ◽

...

Keyword(s):

Kinase Inhibitor ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Line Treatment ◽

Second Line ◽

Saint Louis ◽

Significant Difference ◽

Third Line ◽

Egfr Mutated ◽

Third Line Treatment

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. Methods: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. Results: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53–37.6) and the median follow-up duration was 40.83 months (range 11.33–88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.

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Expert Opinion on the Treatment of Refractory Chronic Phase Chronic Myeloid Leukaemia

European Oncology & Haematology ◽

10.17925/eoh.2017.13.01.17 ◽

2017 ◽

Vol 13 (01) ◽

pp. 17

Author(s):

Tim Hughes ◽

Giuseppe Saglio ◽

◽

Keyword(s):

Chronic Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Second Generation ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Molecular Response ◽

Line Treatment ◽

T315i Mutation ◽

Third Line ◽

Third Line Treatment

The development and clinical availability of second-generation tyrosine kinase inhibitors (TKIs) for the treatment of patients who discontinue imatinib therapy has further improved the outlook for patients with chronic phase chronic myeloid leukaemia (CP-CML). There is, however, uncertainty surrounding how best to treat patients after failing second-generation TKIs. A three-section questionnaire was devised by chronic myeloid leukaemia experts to address questions surrounding this issue. Responses were received from 14 out of 34 experts (41.2%). Generally, a reasonable consensus was found among the responses for most issues. There was a complete consensus that ponatinib was suitable for all patients carrying the T315I mutation regardless of the molecular response to prior treatment. There was also complete consensus that allografting is appropriate in any patient who has had blast crises and is back in a second chronic phase. More recommendations for third-line treatment of CP-CML patients are necessary.

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