Neha Pathak

Purpose Decision-making for chemotherapy in early breast cancer (EBC) in OA (older adults: age ≥ 65 years) is complex due to frailty, multimorbidity, and competing risks for mortality. Magnuson (2021) developed a chemotherapy toxicity prediction score, CARG-BC; its external validation can improve generalizability. Objectives CARG-BC’s ability to predict grade 3 + chemotoxicity in OA with EBC (primary), unplanned healthcare use, and changes to chemotherapy protocol (secondary). Methods A single center retrospective cohort study comprising OA with EBC who received (neo) adjuvant chemotherapy from 2013–2023. Clinical, demographic, CARG-BC, and healthcare usage variables were extracted from patient records. Risk groups based on CARG-BC score were compared using T-test (continuous variables) & χ2 test (categorical variables). Toxicity risk based on CARG-BC score was assessed using logistic regression. The predictive ability of the CARG-BC score was evaluated by calculating AUC. Results Of 243 patients, the median age was 70 years (range 65–86), 99.6% female, 80.2% with comorbidities, 33.7% with polypharmacy, 28.8% living alone, and 8.2% seen in the geriatric oncology clinic. Over half (53.9%) had grade 3 + toxicities. Healthcare utilization included 19.8% of patients with at least one unplanned clinic visit, 29.6% an emergency care visit, and 14.4% a hospitalization. The median CARG-BC score was 7 (IQR 3, 8) and the CARG-BC AUC was 0.76 (95% Confidence interval [CI] 0.70, 0.82). The odds of grade 3 + toxicity is increased by 1.33 times per CARG-BC point increase. Conclusion The CARG-BC model retained good discrimination for grade ≥ 3 chemotoxicity and should be used in shared-decision-making with OA.

The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified front-line regimens, with FLAURA2 demonstrating improvement in PFS with the addition of chemotherapy to Osimertinib and MARIPOSA, showing both a PFS and OS benefit with a novel combination regimen of Amivantamab and Lazertinib. However, these regimens are associated with significantly higher toxicity to patients and pose a huge financial and logistical burden to the health care system; therefore, treatment selection must therefore be individualized, considering disease biology, patient fitness, and toxicity burden. Post-progression strategies remain challenging due to resistance mechanisms like EGFR C797S mutations and MET amplification and the lack of data post-progression on novel first-line combinations. Ongoing trials are investigating fourth-generation EGFR TKIs, MET inhibitors, antibody–drug conjugates, and bispecific antibodies in subsequent lines. While regimens like Amivantamab-Lazertinib show promise even in second-line settings, toxicity, cost, and access remain barriers. As therapeutic options expand, biomarker-driven sequencing and personalized care will be critical to optimizing long-term outcomes in EGFR-mutated mNSCLC.

The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified frontline regimens with FLAURA2 demonstrating improvement in PFS with addition of chemotherapy to Osimertinib and MARIPOSA showing both a PFS and OS benefit with a novel combination regimen of Amivantamab and Lazertinib. However, these regimens are associated with significantly higher toxicity to patients and pose a huge financial and logistical burden to the health care system, therefore, treatment selection must therefore be individualized, considering disease biology, patient fitness, and toxicity burden. Post-progression strategies remain challenging due to resistance mechanisms like EGFR C797S mutations and MET amplification and lack of data post progression on novel 1st line combinations. Ongoing trials are investigating fourth-generation EGFR TKIs, MET inhibitors, antibody-drug conjugates, and bispecific antibodies in subsequent lines. While regimen like Amivantamab-Lazertinib show promise even in second-line settings, toxicity, cost, and access remain barriers. As therapeutic options expand, biomarker-driven sequencing and personalized care will be critical to optimizing long-term outcomes in EGFR-mutated mNSCLC.

Background: The use of cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) with endocrine therapy (ET) is a first-line standard treatment for hormone receptor-positive (ER+) Human Epidermal Growth factor Receptor-2-negative (HER2-) advanced breast cancer. The data supporting incorporation of CDK 4/6i + ET beyond progression are variable. Here, we report a pooled analysis of this strategy. Methods: A systematic review identified reports of both observational and clinical studies, which evaluated the continuation of CDK4/6i beyond progression. The mean overall response rate (ORR) and progression-free survival (PFS) weighted by the study sample size were calculated. Meta-regression comprising linear regression weighted by the sample size (mixed effects) was performed to explore the association between disease and treatment-related factors and the benefit from continuing CDK4/6i. Quantitative significance was assessed using the Burnand criteria. Results: Thirteen studies comprising 1530 patients were included. The median age was 58 years, 50.8% had visceral metastases, and 48% had ESR1 mutations; the median lines of prior therapies were 1 (range 1–5), and 96.3% received palbociclib as the initial CDK4/6i. Eight studies tested a CDK4/6i switch as the intervention. The median PFS was 5.3 months, and the ORR was 14%. In randomized studies, statistically significant differences were observed between CDK4/6i continuation and control, although it is uncertain whether the magnitude of the effect is clinically meaningful. Increasing age, lack of prior chemotherapy, no visceral metastasis or ESR1 mutations, and a switch to a non-palbociclib CDK4/6i were associated with better outcomes. Conclusion: Continuing a CDK 4/6i + ET beyond progression yields modest benefits. Switching CDK4/6i likely results in improved ORR and PFS. Continuing palbociclib beyond progression is likely ineffectual.

Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown. Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel–Haenszel method for adverse events (AEs) with Review-Manager version-5.4. NMA was executed using WINBUGS (Microsoft Excel). Three molecular subgroups were analyzed: HER2-low, PI3K/AKT/mTOR, and the ESR1 mutation subgroup for selective estrogen receptor degrader (SERD). Results: A total of 14 studies were included. In the HER2-low group, Sacituzumab govitecan and trastuzumab deruxtecan had a similar efficacy (HR, 95% CI): PFS (0.98; 0.63–1.43) and OS (1.08; 0.76–1.55). In PI3K/AKT/mTOR-altered cases, capivasertib was superior to alpelisib PFS (0.77; 0.53–1.12), and OS (0.80; 0.48–1.35). SERDs had worse PFS and OS versus ongoing CDK 4/6i (ribociclib). Conclusion: No therapy emerged as the unequivocal choice in the post-CDK 4/6i domain in unselected subgroups. In the HER2-low population, a similar efficacy and different toxicity spectrum was seen. In AKT-altered tumors, capivasertib was less toxic than alpelisib. PROSPERO ID: CRD4202236412.

Introduction: Next-generation sequencing (NGS) has paved the way for precision oncology in oncology clinics today. With rapidly advancing therapeutics, it is becoming increasingly important to obtain information about the molecular milieu of a patient's tumor. However, reporting and interpreting of NGS is fraught with complexity and variability. To understand the questions surrounding NGS reporting in India, we conducted a survey. Objectives: The aim of this study was to assess the gaps in NGS reporting and interpretation in Indian medical oncology clinics. Materials and Methods: An anonymized 10-question survey-based study among Indian medical oncologists through Google forms was conducted between October 4 and 8, 2022. Results: The sample size was n = 58. Seventy-one percent felt there was heterogeneity in NGS reporting, 72% were unaware of NGS reporting guidelines, and 62% did not feel the need for a molecular scientist assist in NGS interpretation. Almost all (98%) felt there was a need for uniform NGS reporting as well as an Indian NGS repository and data-sharing system (93%). Conclusion: Our survey highlights the need for a uniform national guideline concerning NGS reporting.

A woman in her 20s presented with headache and back pain and was found to have a left renal mass with bony metastases. She underwent nephrectomy, and on histopathology was initially diagnosed with stage 4 clear cell sarcoma of the kidney. She underwent palliative radiation and chemotherapy; however, the disease progressed and she came to our centre. We started her on second-line chemotherapy and submitted her tissue blocks for review. Due to her age and lack of sclerotic stroma in the tissue, we had our doubts about the diagnosis and hence, tissue sample was submitted for next-generation sequencing (NGS). NGS detected an EWSR1::CREBL1 fusion, clinching the final diagnosis of sclerosing epithelioid fibrosarcoma of the kidney, a singular diagnosis rarely reported in the literature. Currently, the patient is post her third line of chemotherapy, is on maintenance, and is doing well and has resumed her daily activities.

PURPOSE: Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. PATIENTS AND METHODS: We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). RESULTS: Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. CONCLUSION: It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.