We conducted a large international nested case-control study including 1,881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n=647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer and melanoma) and controls (n=1,234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR=1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had twofold higher risk of non-melanoma (NM) skin cancer (OR=2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR=3.74, 95% CI 1.00-14.01), ruxolitinib (OR=3.87, 95% CI 1.18-12.75) and for drug combination (OR=3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

Background: The steroidal aromatase inactivator exemestane has demonstrated activity after prior failure of non-steroidal aromatase inhibitors (including third-generation inhibitors letrozole and anastrozole) in postmenopausal women with advanced breast cancer. If exemestane is used as first anti-aromatase agent, however, it is unclear whether patients can still benefit from letrozole or anastrozole after progression. Patients and Methods: Postmenopausal patients with advanced, hormone receptor-positive or -unknown breast cancer were eligible for this study. Patients with no prior exposure to anti-aromatase drugs received exemestane, 25 mg daily, as first anti-aromatase agent. At the time of progression, patients were crossed-over to anastrozole or letrozole if further endocrine therapy was considered appropriate. Patients with prior exposure to anti-aromatase agents were also included in the study, and were given anastrozole or letrozole if they had previously received exemestane, or exemestane if they had previously received anastrozole or letrozole. The primary endpoint of the study was the clinical benefit rate (complete response + partial response + stabilization of disease for ≧24 weeks). Results: Forty patients received exemestane 25 mg daily as first anti-aromatase agent, with a CB rate of 67.5% (95% CI 52.9–82.0%) and a median time to progression (TTP) of 9.6 months. In 18 patients, letrozole (n = 17) or anastrozole (n = 1) were used after failure of exemestane: the CB rate was 55.6% (95% CI 32.6–78.5%) with a median TTP of 9.3 months. In 23 patients, exemestane was used after failure of letrozole or anastrozole: the CB rate was 43.5% (95% CI 23.2–63.7%) with a median TTP of 5.1 months. Conclusions: Our study confirms that exemestane is active after prior failure of letrozole or anastrozole. We have also shown that patients can receive exemestane as their first anti-aromatase agent and still benefit from letrozole or anastrozole after progression. This suggests that the partial non-cross resistance between steroidal and non-steroidal anti-aromatase agents is independent of the sequence employed.

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Objectives: Maintenance hormone therapy after first-line chemotherapy is routinely used by many clinicians in advanced breast cancer patients with potentially hormone-sensitive tumors, although there are insufficient evidences in the literature to support this practice. We investigated the effects of the third-generation aromatase inhibitor letrozole as a maintenance therapy in postmenopausal patients who had responded or had stable disease with first-line chemotherapy. Methods: Fifty-eight patients (median age 62 years, range 31–80) were recruited and received letrozole, 2.5 mg/day starting within 8 weeks since the last cycle of chemotherapy. Estrogen and/or progesterone receptor status was positive in 81% of the patients, unknown in 19%; 57% of the patients had visceral disease. First-line chemotherapy included anthracyclines and/or taxanes in 74% of cases. Results: The median time to progression (TTP) from starting letrozole was 18.5 months. A shorter TTP was found in patients with abnormal CA 15-3 levels at the start of maintenance letrozole (median TTP, 9.9 months: p = 0.01), or with levels increasing >25% from baseline during the first 6 months of letrozole therapy (median TTP, 8.2 months: p < 0.0001). Response status improved during letrozole in 15.5% of patients who had obtained less than a complete response to chemotherapy. Maintenance treatment was well tolerated and had no significant impact on quality of life scores. Conclusions: This study provides evidence in support of the common clinical practice of maintenance hormone therapy after chemotherapy in suitably selected patients with advanced breast cancer.

by IRC. Overall survival (OS) and modified progression-free survival (mPFS; time to progression, death, or subsequent Tx) were exploratory endpoints. PFS was a post hoc analysis.Results: Fifty-one pts were treated (median age 37 y); minimum followup was 24.4 mo at data cut-off. Other baseline characteristics have been previously described (Ramchandren R et al. EHA 2018). Monotherapy was completed by 49/51 (96%) pts, combination Tx by 45/50 (90%); 48 pts entered follow-up. After 2 combination cycles, CR rate was 51% per IRC (71% CMR) and 71% per investigator; at EOT, CR rate was 69% (75% CMR) per IRC and 80% per investigator. At 21 mo, mPFS rate per investigator was 80% (95% CI, 66-89) and PFS rate per investigator was 83% (95% CI, 69-91; Figure). Overall, 30 (59%) pts experienced grade (G) 3-4 TRAEs, most commonly neutropenia in 21 (41%). The most common G 3-4 immune-mediated AE was hepatitis (2 pts, 4%). No G 5 TRAEs occurred ≤ 30 d from last dose; 2 deaths were reported during the extended follow-up: 1 pt (aged 68 y) died 38 d after last dose due to study drug toxicity; another (aged 85 y) died 451 d after last dose due to disease progression. Conclusions: With extended follow-up, nivolumab followed by N-AVD demonstrated a 21-mo PFS rate of 83% per investigator, a high metabolic response rate with 75% CMR at EOT per IRC, with no new safety signals. Incorporation of Deauville assessment improved the concordance of CR between IRC-and investigator-assessed responses. Nivolumab followed by N-AVD provides a promising alternative Tx option in newly diagnosed AS cHL. ABSTRACT 147 Introduction: Consolidation Radiotherapy (cRT) was originally proposed for ABVD-treated advanced stage Hodgkin Lymphoma (aHL) presenting with bulky or a residual mass (RM) after ABVD. However, very few published data exist on the role of cRT on RM in patients (pts) with a negative end-of treatment PET (EoT-PET) after ABVD. Methods: In the HD0607 clinical trial (Gallamini JCO 2018) aHL pts (stage IIB-IVB) were treated with 2 ABVD courses, followed by an interim PET (PET-2). PET-2 positive pts were randomized to 4 BEACOPP escalated + 4 BEACOPP baseline cycles ± rituximab before each cycle. PET-2 negative pts were treated with 4 more ABVD and a EoT-PET was performed afterwards. PET-2 and EoT-PET negative pts were randomized to either cRT on the sites where a large nodal mass (LNM) was detected at baseline, or no further therapy (NFT). LNM was defined as single or a conglomerated nodal mass with the largest diameter ≥ 5 cm in baseline CT. Results: After ABVD, 47/630 (7%) PET2 negative pts with a positive EoT-PET, 27/630 off study pts for disease progression or consent withdrawal and 260 pts without LNM were not suitable for the random, while 296 were randomized to cRT (148) or NFT (148). In this pts cohort the largest diameter of LNM was 5-7 cm in101 (34%) 8-10 cm in 96 (32%), while a classical bulky (diameter >10 cm) was detected in 99 (33%) pts. Prognostic factors, age, sex, stage, IPS, Performance status, extra-nodal sites, bulky disease were ...