Patients with platinum-resistant ovarian cancer (PROC) have limited therapeutic options and poor survival. There is a need for the development of newer therapies. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor with antitumor activity in preclinical models of PROC. Synergism with conventional cytotoxic agents like etoposide has been demonstrated. In this prospective, single-arm, open-label, phase 2 study, we included patients ≥ 18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral VPA 60 mg/kg/day in three divided doses for 3 days (D1-D3), followed by oral etoposide 50 mg once daily for two consecutive weeks (D4-D17). Serum samples were collected to assess peak VPA drug levels. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. We sought to show an improvement in response rate from 25% (historically with oral etoposide) to 40% with the addition of VPA. 27 patients were enrolled in the study, and 18 [median age: 52 (45-59) years; serous histology:17 (94%); ECOG-PS 2 or 3: 14 (78%)] were evaluable for the response after 4 months. Nine patients were lost from follow-up before achieving the primary endpoint (mainly due to Covid-related lockdown issues). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients [clinical benefit rate (CBR) of 11%]. The median OS and PFS were 7 months and 2 months, respectively. Grade ≥ 3 adverse events were reported in 6 (33%) patients. The addition of valproic acid to oral etoposide in patients with PROC and poor general condition was not helpful and failed to improve responses compared to those historically achieved with single-agent etoposide. However, further phase 2 randomized controlled trials with larger sample size can be done to confirm the findings.

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Background Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with poor prognosis and access to anti-HER2 treatment is still a challenge in lower-middle income countries. The availability of the biosimilar trastuzumab has improved access by lowering the costs. We report the pattern of use of neoadjuvant ± adjuvant trastuzumab and outcomes in patients with HER2-positive non-metastatic breast cancer treated with regimens incorporating shorter durations of therapy and the use of the biosimilar trastuzumab compared to the innovator. Methods We conducted a retrospective analysis of patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant ± adjuvant trastuzumab (innovator ( n = 34 (33%)) and biosimilar ( n = 70 (67%)) manufactured by Biocon Biologics) with chemotherapy. Information regarding chemotherapy regimens, duration of trastuzumab use (≤12 weeks and >12 weeks), pathological response (Miller Payne grade), disease free survival (DFS), overall survival (OS) and safety data were collected from electronic medical records. Results A total of 135 patients were analysed with a median age of 51 years (range: 23–82); of these, 57% were postmenopausal, 31.8% were hormone receptor positive and 62.9% had stage III disease. The overall pathological complete response (p-CR) in both breast and axilla increased to 37.6% in patients treated with trastuzumab preoperatively as compared to 22.2% in patients who did not receive any trastuzumab. Patients receiving innovator trastuzumab and biosimilar trastuzumab showed a p-CR of 28.5% and 41.7%, respectively. At a median follow-up of 42 months (range: 3–114), there were 18 relapses and 11 deaths. The 3-year DFS was 87.1% and OS was 92.2%. Cardiac dysfunction developed in 4 of 78 (5.1%) evaluable patients. Conclusion Access to anti-HER2 therapy in the treatment of non-metastatic HER2-positive breast cancer in resource-constrained settings has improved significantly with the availability of the biosimilar trastuzumab. Imbalances in patient profiles at baseline in routine clinical practice led to inconclusive outcomes of ≤12 weeks versus >12 weeks trastuzumab treatment. However, on the basis of historical data, patients could be offered shorter duration of trastuzumab when a standard 1-year treatment of adjuvant trastuzumab is not feasible in resource-constrained settings. The p-CR using the biosimilar trastuzumab in neoadjuvant treatment has been observed to be comparable to the innovator trastuzumab.

Purpose In a developing country like India, genomic data sets for even the most clinically relevant genes like BRCA1 and BRCA2 is rather scarce. Also, there is a need to identify and screen population specific BRCA hotspots to pave a way for affordable genetic testing strategies in clinical practice. Method This is an ambispective study to evaluate an NGS based approach to identify pathogenic variants in BRCA1 and BRCA2 genes among 430 patients with Breast and Ovarian cancers. The target enrichment was carried out using the in-house designed Multiplex-PCR followed by targeted Next-generation sequencing (NGS) for BRCA1 and BRCA2. Also, allele-specific PCR based genotyping of del185AG was carried out in additional 120 patients. Results In this study, we have identified 100 BRCA1 and BRCA2 variants and based on ACMG 2015 guidelines, these variants were classified as 46 pathogenic, 9 likely pathogenic, and 45 VUS. Of these variants, three were novel, two with likely pathogenic, and one variant of uncertain significance (VUS). The 185delAG was identified as a recurrent mutation in the Southern Indian population accounting for 25.45% of the pathogenic variants. In addition, a family history of cancers of the breast, ovary, pancreas, or prostate (BOPP) was found to be associated with a higher risk of identifying a deleterious BRCA1/2 variant [OR 3.2 (95%CI 1.84–5.77) p ≤ 0.001]. Conclusions These results suggest that Multiplex PCR-NGS is a sensitive and specific strategy for BRCA testing. However, ASPCR-based genotyping of BRCA1(NM_007300.4): c.68_69del followed by targeted NGS would be a cost-effective approach in south Indian patients.