Outcomes of patients in the North Trent region with advanced non-small-cell lung cancer treated with maintenance pemetrexed following induction with platinum non-pemetrexed doublet chemotherapy Marshall R, Kakoudaki M , Danson S.J, Fisher P.M, Hatton M.Q, Lee C.E, Das T, Bates E, Woll P.J, Taylor F Weston Park Hospital, Sheffield, United Kingdom S10 2SJ Background In March 2010, NICE recommended maintenance pemetrexed following induction treatment with platinum non-pemetrexed doublet chemotherapy in locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) following evidence demonstrating superior progression-free-survival (PFS) (4.3 months vs 2.6 months) and overall-survival (OS) (13.4 months vs 10.6 months) compared to placebo1. Aims Primary aim: Review outcomes of patients who received maintenance PMTX for NSCLC in the North Trent region to include PFS and OS. Secondary aims: Establish rates of toxicity and the nature of adverse effects and ascertain prognostic factors for treated patients. Methods Patients who commenced 3-weekly maintenance pemetrexed (500mg/m2) following induction platinum non-pemetrexed doublet chemotherapy between January 2013 and July 2015 were identified using an electronic database. Figure 1: Pie chart showing response to induction chemotherapy Table 3: Survival Median PFS (months) 5.5 (range 0.2-22.9) OS (months) 10.5 (range 1.0-36.9) Patients alive at 1 year post PMTX 49% Best responses to PMTX are shown in Figure 2. 4 patients (7%) demonstrated PR and 42 patients (73%) SD. 7 patients (12%) progressed on maintenance (DP) and for 4 patients (7%) the response was unknown. Results – Demographics 57 patients were identified Patients with a radiological response of PR or SD to PMTX had a significantly longer PFS and OS compared to those who did not respond (Figure 3). Figure 2: Bar chart showing response to PMTX Table 1: patient demographics % patients treated Median age in years (range) 66 (31-79) Gender: Female Male n (%) 28 (49) 29 (51) Histology: Adenocarcinoma Adeno-squamous carcinoma Poorly differentiated NSCLC Broncho-alveolar carcinoma Recurrent NSCLC Neuroendocrine Squamous n (%) 44 (77) 3 (5) 6 (11) 2 (4) 1 (2) 0 (0) Stage: IV IIIb IIIa Unknown 50 (88) 5 (9) Induction regimen: Gemcitabine/carboplatin Gemcitabine/cisplatin Gefitinib Cisplatin/vinorelbine 51 (89) 4 (7) Performance status 1 unknown (n) (%) 22 39 30 53 5 8 Results- Toxicity Treatment toxicity were recorded using criteria for adverse events version 4 (CTCAEv4). 93% of patients reported toxicity of grade I-III. Table 2 displays toxicities. 25% of patients discontinued treatment due to toxicity. No patients experienced grade 4 toxicity. Toxicity data was not available for 2 patients. Table 2: Worst toxicity reported CTCAEv4 Figure 3: Kaplan-meier curve of PMTX PFS and OS in responders and non-responders Grade I (%) II (%) III (%) Toxicity Nausea Vomiting Fatigue Skin rash Mucositis Diarrhoea Constipation Peripheral oedema Alopecia Infection Neutropenia Anaemia Thrombocytopenia Liver dysfunction Renal dysfunction 33 4 28 7 19 11 12 2 9 18 16 21 5 Patients >70 years had significantly longer PFS than patients <70 years, but there was no significant difference in OS (Figure 4). The reasons for which remain unclear and numbers of cases in this study are limited. Results- Response rate Radiological response to induction chemotherapy was assessed and no patient had progressive disease prior to commencing maintenance treatment (n=57). Results show a complete response (CR) rate of 1.8%, a partial response (PR) rate of 54% with 42% of patients demonstrating stable disease (SD) (Figure 1) Table 2: Figures denote percentage of patients reporting each adverse event Results- Survival Median OS was was calculated using the date of first maintenance PMTX treatment to date last known to be alive or last follow up appointment PFS was calculated from day 1 of PMTX to until date of radiological disease progression. Figure 4: Kaplan-meier curve of PMTX PFS and OS <70 years and >70 year olds Conclusion Maintenance PMTX in our patient cohort generates survival rates similar to that of previously published data1. Longer PFS was significantly associated with response to PMTX and age >70 years on commencing chemotherapy. Whilst PMTX was reasonably well tolerated with no patients reporting grade 4 toxicity, toxicity related drug discontinuation in this patient cohort is higher than published work1. References: 1.Cileanu et al . Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind phase-3 study. Lancet. (2009);374:1432-40.