Real-world outcomes according to treatment strategies in ALK-rearranged non-small-cell lung cancer (NSCLC) patients: an Italian retrospective study.

PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received. PATIENTS: We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions. RESULTS: After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9-11.2] and 11.1 months [CI 95% 9.2-13.8], respectively, while TTF were 10.2 [CI 95% 8.5-12.6] and 11.9 months [CI 95% 9.7-17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8-54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0-73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6-NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3-34.0)] (P < 0.0001). CONCLUSION: The sequential administration of crizotinib and a new generation ALKis provided a remarkable clinical benefit in this real-life population, being an interesting option to consider in selected patients.

Chemotherapy-induced nausea and vomiting (CINV) in patients with advanced lung cancer during the first-line treatment: assessment by physicians, nurses, and patients from an Italian multicenter survey.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) still represents a common side-effect of chemotherapy, and often, its perception differs between patients and healthcare professionals. The aim of this study was to evaluate the agreement on the perception of CINV and other items among clinicians, patients, and nurses. METHODS: This observational prospective study was part of an evaluation program promoted by the Women Against Lung Cancer in Europe (WALCE) Onlus. From August 2015 to February 2016, a survey was administered in 11 oncologic institutions to 188 stage IV lung cancer patients and to their oncologists and nurses during first-line chemotherapy. Our survey investigated 11 aspects: anxiety, mood, weakness, appetite, nausea, vomiting, pain, drowsiness, breath, general condition, and trust in treatments. These items were assessed through Numerical Rating Scale at four consecutive evaluations: at T0 (immediately prior to the first cycle), at T1 (immediately prior to the second cycle), at T2 (immediately prior to the third cycle), and at T3 (immediately prior to the fourth cycle). Clinician versus patient (CvP), nurse versus patient (NvP), and clinician versus nurse (CvN) agreements were estimated applying Weighted Cohen's kappa. A multivariate logistic model and generalized equation estimates were applied to evaluate factors possibly influencing CINV development. RESULTS: The incidence of patients reporting CINV varied from 40% at T0 to 71% at T3. Both CvP and NvP agreement on the investigated items were mainly moderate, slightly increasing over time, and becoming substantial for some items, in particular for NvP. Pre-chemotherapy anxiety in its mild, moderate, and severe manifestations, as well as mild, moderate, and severe anxiety experienced after chemotherapy start, exposed patients to a higher risk of anticipatory and acute/delayed CINV, respectively. CONCLUSIONS: Despite clinical staff awareness of patients' status and perceptions, CINV still represents a clinical problem. This study confirms that particular attention should be paid to anxiety due to its key role in CINV development.

Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide, followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification.

PURPOSE OF THE STUDY: Trastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response (pCR). Non-pegylated liposome-encapsulated doxorubicin (NPLD) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC. METHODS: Preoperative treatment included NPLD (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Clinical staging was exploratory evaluated by CT-PET. RESULTS: 43 pts were treated from december 2005 to September 2011, 39 of them were evaluable for the purpose of study. Median age was 53 years (range: 31-78), the majority of pts had tumour stage cT2 (63%), tumour grade 3 (86%), clinical nodes involvement N+ (77%), ER positive (56%) and Ki-67 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. There was an association between Ki-67 ≥20% at baseline and pCR (p = 0.018). No cardiac toxicity or discontinuation of trastuzumab was reported. CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes. CONCLUSIONS: This study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active. NPLD is a safe option to minimize cardiotoxicity.

A multicenter, randomized comparative trial of the clinical effects on cycle control of two 21-day regimens of oral contraceptives containing 20 µg EE.

Purpose: This multicenter, randomized, open-label comparative study was designed to evaluate the effects on cycle control of the only two oral contraceptives (OCs) containing 20 µg ethinyl estradiol (EE) that are available in North America.Methods: Women of childbearing age who desired OCs for birth control were eligible to enroll in this study. Sixty-two subjects were randomly assigned to receive Alesse (levonorgestrel 0.1 mg and EE 20 µg) or Loestrin Fe 1/20(R) (norethindrone acetate 1.0 mg and EE 20 µg).Results: At the time of the interim analysis data cut-off 32 subjects had completed 3 cycles of Alesse and 30 had completed 3 cycles of Loestrin Fe 1/20. The groups were similar with regard to age, weight, height, race, and prior OC usage. A total of 22% of the subjects in the levonorgestrel group and 27% of those subjects in the norethindrone group had never used OCs. The remainder had not used OCs for at least 3 months before entering the trial. During the third cycle of use, the percentage of normal cycles was significantly greater in the levonorgestrel group (P <.05). Moreover, the rate of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone group (62.9%) was more than double that in the levonoregestrel group (29.0%). Cumulatively, from cycles 1 to 3, there was a higher incidence of absence of withdrawal bleeding with norethindrone when compared with levonorgestrel (27.7% vs 5.3%).Conclusion: The results of this study demonstrate that good cycle control can be achieved with an OC containing 20 µg EE. The superior cycle control of Alesse compared with Loestrin Fe 1/20 is consistent with that found in comparative studies of the cycle control of levonorgestrel, norethindrone, and norethindrone acetate containing OCs that had a higher dose of EE.