Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad range of advanced solid tumors.

Objective The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.gov NCT01078662) have been reported previously. Methods Eligible patients were treated with oral olaparib 400 mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated. Results In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26–42) and median DoR was 7.9 (95% CI 5.6–9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2 months (95% CI 5.6–13.5) compared with 8.0 months (4.8–14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib. Conclusion Following ≥3 prior lines of chemotherapy, olaparib 400 mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.

Background Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA -mutated ( BRCA m) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2 . We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type ( BRCA wt) tumours. Methods Tumour samples from an olaparib maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification of mutations in genes involved in homologous recombination repair (HRR), BRCA1 promoter methylation status, measurement of BRCA1 protein and Myriad HRD score. Results Patients with BRCA m tumours gained most benefit from olaparib; a similar treatment benefit was also observed in 21/95 patients whose tumours were BRCA wt but had loss-of-function HRR mutations compared to patients with no detectable HRR mutations (58/95). A higher median Myriad MyChoice ® HRD score was observed in BRCA m and BRCA wt tumours with BRCA1 methylation. Patients without BRCA m tumours derived benefit from olaparib treatment vs placebo although to a lesser extent than BRCA m patients. Conclusions Ovarian cancer patients with tumours harbouring loss-of-function mutations in HRR genes other than BRCA1 / 2 may constitute a small, molecularly identifiable and clinically relevant population who derive treatment benefit from olaparib similar to patients with BRCA m.

Vaccination against influenza and Streptococcus pneumoniae is recommended for elderly and immunocompromised individuals. However, there is little information concerning the efficacy of vaccination in specific groups of patients. In this study, 52 patients underwent vaccination against influenza, S. pneumoniae and Haemophilus influenzae type b (Hib) as they attended hospital outpatient clinics. Serum was analysed prior to vaccination and 4–6 weeks afterwards. Antibody titres against S. pneumoniae and Hib were compared with reference values corresponding to the geometric mean titres of a healthy UK population. For influenza vaccination, haemagglutination inhibition (HI) titres were measured against three inactivated strains; a titre of ≥ 1/40 was considered protective. No patient had protective titres to all three antigens prior to vaccination and 41 patients (85%) had titres < 1/40 to all 3 strains. Post vaccination only 9/48 patients (19%) achieved protective antibody titres. Resistance to S. pneumoniae and response to Pneumovax II was also poor: prevaccination, 45 patients (93%) had suboptimal antibody titres and in 26/43 patients (61%) titres remained low post vaccination. Resistance to Hib and response to vaccination was comparable with the healthy adult UK population. These results question the practice of routine influenza and pneumococcal vaccination in myeloma patients. © 2000 Cancer Research Campaign

NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662.