1. 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 )
OS (months)
10.5
(range )
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: