The clinical utility and safety of short-course immune checkpoint inhibitors in multiple tumours-A real-world multicentric study from India.

The real-world data on short course of immune checkpoint inhibitor (ICI) use are sparse and merit exploration. A multicentric observational study on the safety and efficacy of ICI in oncology patients between August 2014 and October 2020 involves 1011 patients across 13 centers in India. The median age was 59 (min 16-max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles was 5 (95% confidence interval [CI] 1-27), and the median duration of therapy was 3 (95% CI 0.5-13) months. ICIs were used commonly in the second and third line setting in our study (66.4%, n = 671). Objective response rate (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease, and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n = 906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow-up of 14.1 (95% CI 12.9-15.3) months, there were 616 events of progression and 443 events of death, and the median progression free survival and overall survival were 6.4 (95% CI 5.5-7.3) and 13.6 (95% CI 11.6-15.7) months, respectively, in the overall cohort. Among the immune-related adverse events, autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common. Real-world multicentric Indian data predominantly with short-course ICI therapy have comparable efficacy/safety to international literature with standard ICI therapy.

Multicentric real world evidence with palbociclib in hormone positive HER2 negative metastatic breast cancer in Indian population.

The combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2- MBC). Several randomized trials have shown the benefits of this combination, however, real world evidence in the Indian patients is warranted. The present study reports the largest real world multicentric data from Indian population on the use of Palbociclib in HR+/HER2- MBC. A multicentric study on the HR+/HER2- MBC patients who received palbociclib with hormonal agent (Aromatase inhibitors/Fulvestrant) between February 2017 and May 2020 was conducted. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Among a total of 188 patients, 57% patients were premenopausal and 17% patients had bone only disease. Altogether, 115 (61%) patients received palbociclib with Aromatase inhibitors in the first line whereas 73 (39%) patients received it in the second line with Fulvestrant. The median follow up period with advanced disease was 13 months. The median progression free survival in the first line and second line was 20.2 months and 12 months, respectively (p-value < 0.0001). The objective response rate was 80% and 47.9% in first and second lines, respectively. Dose interruptions/ discontinuation were done in 14.9% and 2.7% patients in the first and second lines, respectively. In terms of toxicity, 10% patients had grade 3-4 adverse events. The present real world data of the use of palbociclib in Indian population suggests similar effectiveness to previously published real world evidences and has been adapted as the standard of care in the first and second line treatment of HR+/HER2- MBC.

PARP Inhibitor in Platinum-Resistant Ovarian Cancer: Single-Center Real-World Experience.

PURPOSE: Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven efficacy in treatment of BReast CAncer (BRCA) gene mutation-positive platinum-sensitive ovarian cancers. There is paucity of data for their role in platinum-resistant ovarian cancer (PROC). We report here retrospective analysis of outcome of PARPi treatment in a group of patients including those of PROC. PATIENTS AND METHODS: We analyzed all consecutive patients who received PARPi. The efficacy of PARPi monotherapy was assessed in patients with relapsed high-grade serous ovarian carcinoma with gBRCAm. The drug was procured through compassionate program. Drugs (olaparib and talazoparib) were provided in capsule form. RESULTS: Between July 1, 2015, and June 30, 2019, 28 patients with ovarian cancer received PARPi. At the time of data censoring (September 30, 2019), four (14.3%) patients are still on treatment. Median age was 54.5 years (range, 39-75 years). Median number of previous lines of chemotherapy received was three (range, 1-6). Eleven platinum-sensitive patients received the drug as maintenance (five in complete response and six in partial response after chemotherapy), whereas 17 (60.7%) had platinum-resistant progressive disease while starting the drug. In PROC, objective response rate (complete response plus partial response) was 47%, median progression-free survival was 8.2 months (5.3-11.3), and overall survival was 14.9 months (11.2-18.5). No new side effects were observed. CONCLUSION: This is the first study from India evaluating PARPi in platinum-resistant ovarian cancer. This study suggests that PARPi is a viable treatment option in patients with PROC with gBRCAm. This should be further evaluated in randomized clinical trial.

Role of Cresp® in the management of chemotherapy-induced anemia in cancer patients: A real-world clinical practice audit.

INTRODUCTION: Anemia is a common, underestimated problem in cancer patients receiving myelosuppressive chemotherapy and has significant adverse effect on the quality of life and outcome. Darbepoetin has been shown to be effective in this setting, but controversy surrounds it actual use. METHODS: We analyzed prospectively collected clinical practice data of patients receiving darbepoetin in a real-world setting for this retrospective audit. Patients with baseline hemoglobin (Hb) of <11 g/dl were included in this analysis. Their medical records were audited using a predetermined 35-point pro forma. RESULTS: There were a total of 274 patients with advanced cancer receiving myelosuppressive chemotherapy who had baseline Hb <11 g/dl and who were given darbepoetin. Head-and-neck squamous cell carcinoma, lung cancer, and breast cancer were the most common cancers. Their median baseline Hb was 8.9 g/dl which rose to 11.2 g/dl at the end of commenced therapy, along with improved symptomatology. There were no new toxicities, and only two patients required discontinuation of darbepoetin due to toxicity. CONCLUSION: Darbepoetin is safe and effective in the prevention and management of anemia among patients receiving myelosuppressive chemotherapy.

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients.

OBJECTIVE: There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. METHODS: In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. RESULTS: A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. CONCLUSIONS: FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent.

Improving the accuracy of target volume delineation by combined use of computed tomography, magnetic resonance imaging and positron emission tomography in head and neck carcinomas.

OBJECTIVE: Conformal radiation therapy mandates accurate delineation of target volumes, which requires incorporation of modern imaging modalities like magnetic resonance imaging (MRI) and positron emission tomography (PET) in addition to conventionally used computed tomography (CT). This can resolve discrepancies in target delineation in head and neck carcinomas resulting in better local control. We hereby report the comparison of Gross Tumor Volumes (GTVs) (primary) drawn using PET, CT and MRI and their concordance indices. METHODS AND MATERIAL: Twenty five patients with head and neck cancer were taken into this study. MRI, PET and CT planning scans were done as per standard guidelines. Three sets of primary GTVs namely GTV- PET, GTV-CT and GTV-MRI were contoured on fused images. All the three volumes and concordances among the volumes were analyzed. RESULT: The mean GTV-CT, GTV-PET and GTV-MRI volumes were 29.65 cc ± 31.27, 32.05 cc ± 33.75 and 24.85 cc ± 25.28 respectively. There was a significant difference in the GTV-MRI & GTV-CT volumes (P = 0.023) and GTV-PET & GTV-MRI volumes (P = 0.049). However, there was no significant difference in the GTV-PET & GTV-CT volume (P = 0.468). The mean CI (PET-MRI), CI (CT-MRI) and CI (PET-CT) was 0.42, 0.46 and 0.47 respectively, which depicts a moderate concordance. CONCLUSION: PET and MRI are useful imaging tools in head and neck malignancies and should be used in conjunction with CT scan for improved target volume delineation.