First line therapies usually induce the longest progression free survival (PFS) in advanced/metastatic cancer as compared to subsequent lines of treatment. However, immunotherapy (IT) due to its mechanisms of action could influence sensitivity to conventional cancer therapy (CCT) after progression to IT and thereby, influence both tumor growth rate (TGR) and progression free survival (PFS). We have studied TGR and PFS before and after participation in phase I IT trials.
We retrospectively studied 173 patients who were enrolled in Phase I IT trials at our institution between January 2012 and September 2017. Patients should have received at least one line of CCT before and after IT. Baseline characteristics (sex, age, tumor type, presence of liver disease, number of CCT lines prior to IT, type of CCT and IT) were recorded. PFS before and after IT was calculated. A ratio of PFS after/before IT (PFSaftIT /PFSbefIT) over 1.2 was considered clinically significant. TGR was calculated based on the formulas: TGR = 100 (exp(TG)−1), TG = 3 Log(Dt/D0)/t.
37 patients met inclusion criteria. Baseline characteristics are shown in the table. Nine of 37 patients (6 CRC, 3 renal cancer) presented a PFSaftIT/PFSbefIT rate over 1.2. Regarding TGR, of 16 patients in whom TGRpre and TGRpost were available, 3 patients (2 CRC, 1 NSCLC) presented a decrease in TGR greater than 15% when given treatment after IT therapy.Table: 1228P
|Characteristics||N = 37|
|Median (M) age at diagnosis (range)||55 (31-79)|
|M lines prior to IT (range)||2 (1-5)|
|Primary tumor Gastrointestinal Genitourinary Gynecological NSCLC Head and neck Breast cancer||19 7 5 4 1 1|
|Presence of liver disease (pre/IT/pro)||15/18/31|
|CCT class (pre/post IT) Platinum derivatives Other alkylating agents (a) Antimetabolites a Anthracyclines Topoisomerase inhibitors (i) Antimicrotubules a Antiangiogenic a Signal transduction i Immunotherapy Others||14/18 0/3 14/21 3/0 13/7 5/4 17/19 1/3 4/1 4/3|
|Combined/monotherapy during IT||22/15|
Our data suggest a better outcome on ensuing systemic therapies after IT. Further prospective investigations are needed to select the subset of patients who are more prone to a re-sensitization to CCT and to understand the mechanisms underlying.
Clinical trial identification
Legal entity responsible for the study
Clínica Universidad de Navarra.
Has not received any funding.
I. Melero: Advisory: BMS, Roche, AstraZeneca, Genmab, Alligator, Tusk, Bioncotech, Merck/Serono. All other authors have declared no conflicts of interest.