RESUMO
OBJECTIVES: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure. MATERIALS AND METHODS: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS). RESULTS: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis. CONCLUSIONS: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.
Assuntos
Acrilamidas , Compostos de Anilina , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Pemetrexede , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Receptores ErbB/genética , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pemetrexede/uso terapêutico , Pemetrexede/administração & dosagem , Platina/uso terapêutico , Platina/administração & dosagem , Pirimidinas , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Ensuring reliable central venous access with the fewest complications is vital for cancer patients receiving chemotherapy. A systematic review and network meta-analysis was conducted to compare the safety, quality of life, and cost-effectiveness of different types of central venous access devices (CVADs) for patients receiving chemotherapy. METHODS: The PubMed, EMBASE, and Cochrane databases were searched from inception to August 20, 2021 for randomized controlled trials comparing the various CVADs (ie, nontunneled central venous catheters [CVCs], peripherally inserted CVCs [PICCs], totally implantable venous access ports [TIVAPs], and tunneled CVCs). RESULTS: A total of 11 eligible randomized controlled trials of 2585 patients were identified. TIVAPs were associated with a lower odds of overall complications, device removal due to complications, and thrombotic and mechanical complications compared with PICCs (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.43-0.69; OR, 0.49; 95% CI 0.26-0.93; OR, 0.37; 95% CI, 0.23-0.62; and OR, 0.35; 95% CI, 0.13-0.95, respectively). Tunneled CVCs were associated with a higher odds of overall complications, device removal due to complications, and infective complications compared with TIVAPs (OR, 1.68; 95% CI, 1.30-2.17; OR, 2.52; 95% CI, 1.34-4.73; and OR, 2.11; 95% CI, 1.14-3.90, respectively). The ranking probability using the surface under the cumulative ranking curve values indicated that TIVAPs had the lowest probability of overall complications, removal due to complications, and thrombotic complications. CONCLUSIONS: TIVAPs were found to be superior in terms of complications and quality of life compared with other CVADs, without compromising cost-effectiveness, and should be considered the standard of care for patients receiving chemotherapy.