Merck Serono GmbH

This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany.

Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle).

Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP.

This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.

Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials.

We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper–Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in < 10% of patients; otherwise, a normal approximation method was used.

Initially, 1409 publications were identified, of which 318 were excluded during initial screening and 1073 were excluded after full text review for not meeting the inclusion criteria. Eighteen studies (6630 cycles) reported dose adjustment: 5/18 studies (1359 cycles) reported data for an unspecified dose adjustment (direction not defined), in 10/18 studies (3952 cycles) dose increases were reported, and in 11/18 studies (5123 cycles) dose decreases were reported. The studies were performed in women with poor, normal and high response, with one study reporting in oocyte donors and one in obese women. The median day that dose adjustment was permitted was Day 6 after the start of treatment. The point estimates for incidence (95% CI) for unspecified dose adjustment, dose increases, and dose decreases were 45.3% (42.7, 48.0), 19.2% (18.0, 20.5), and 9.5% (8.7, 10.3), respectively.

This systematic review highlights that, in studies in which dose adjustment was allowed and reported, the estimated incidence of r-hFSH dose adjustments during ovarian stimulation was up to 45%.

Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC.

In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0–100), which were summarized to the overall VAS score.

Fourhundred seventy patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (− 2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (− 7.82 vs. non-responders − 1.97, p = 0.0005). The VAS for pain (− 16.37 vs. non-responders − 8.89, p = 0.001) and swallowing of solid food (− 16.67 vs. non-responders − 5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05–1.20, p = 0.0009).

In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.

ClinicalTrials.gov, NCT00122460. Registered 22 Juli 2005,