Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience.

Background: Randomized studies of neoadjuvant (NA) trastuzumab and pertuzumab combined with chemotherapy for HER2-positive breast cancers (BC) have reported pathological complete response (pCR) rates of 39 to 61%. This study aimed to determine the real-world efficacy and toxicity of NA trastuzumab and pertuzumab combined with chemotherapy in a UK tertiary referral cancer centre. Methods: HER2-positive early BC patients given neoadjuvant chemotherapy with trastuzumab and pertuzumab between October 2016 and February 2018 at our tertiary referral cancer centre were identified via pharmacy records. Clinico-pathological information, treatment regimens, treatment-emergent toxicities, operative details, and pathological responses and outcomes were recorded. Results: 78 female patients were identified; 2 had bilateral diseases and 48 of 78 (62%) were node positive at presentation. 55 of 80 (71%) tumours were ER-positive. PCR occurred in 37 of 78 (46.3%; 95% CI: 35.3-57.2%) patients. 14 of 23 (60.8%) patients with ER-negative tumours achieved pCR; 23 of 55 (41.8%) were ER-positive and 6 of 19 (31.6%) were ER-positive and PgR-positive. No cardiac toxicity was documented. Diarrhoea occurred in 53 of 72 (74%) patients. Grade 3-4 toxicity occurred in ≥2% patients. These were diarrhoea, fatigue, and infection. The Median follow up period was 45.2 months (95% CI 43.8-46.3) with 71 of 78 (91.0%) remaining disease-free and 72 of 78 (92.3%) alive. Estimated OS at 2 years 86% (95% CI: 75-99%). Conclusion: This data confirms the efficacy of neoadjuvant chemotherapy combined with dual HER2 directed therapy. While no cardiac toxicity was observed, diarrhoea occurred frequently. The low pCR rate observed in ER and PgR-positive BCs warrants further investigation and consideration of strategies to increase the pCR rate.

Survival following primary surgery for oral cancer.

The main aims of this article are to report the overall and disease-specific survival of a consecutive series of patients presenting with oral cancer from 1992 to 2002 and to relate survival to clinical and pathological factors. The article uses population-based age-sex mortality rates in the North-West of England to highlight differences in overall and disease-specific survival. 541 patients with oral squamous cell carcinoma presented to the Regional Maxillofacial Unit from 1992 to 2002. Curative treatment favoured radical primary surgery, 10% (52) received primary radiotherapy. These patients were on average 8 years older with more advanced tumours and overall poorer survival at 5 years, 23% (SE 7%). The remainder of the results refer to 489 patients who had primary curative surgery, 40% (194) of whom received adjuvant radiotherapy. The overall survival (OS) was 56% (SE 2%) and the disease-specific survival (DSS) was 74% (SE 2%). There was a local recurrence rate of 10% (50) and the loco-regional recurrence rate was 21% (103). The second primary rate was 7% (35). Survival figures had improved over the 10-year period from 63% DSS for the first 4 years of the study (1992-1995) compared to 81% for the last 3 years (2000-2002). In stepwise Cox regression the two predictors selected for disease-specific survival were pN status and margins (both p<0.001). Age-sex mortality rates for the North-West indicate that 15.0% of the 489 primary surgery patients might have been expected to die within 5 years if they were typical of the general population and the observed difference between all causes and oral-cancer specific survival was 18.3%. These data emphasise the value of disease-specific survival as an indicator of successful treatment in a cohort that tends to be elderly, from social deprived backgrounds, with life styles and comorbidity that influence overall survival.