Importance The Cancer Aging Research Group (CARG) toxicity score is used to assess toxicity risk in geriatric patients receiving chemotherapy. Objective The primary aim was to validate the CARG score in geriatric patients treated with curative intent chemotherapy in predicting grade 3–5 toxicities. Design This was a longitudinal prospective observational study. Setting Tata Memorial Hospital, Mumbai, India, a tertiary cancer care referral centre. Participants Patients, aged ≥65 years, with gastrointestinal, breast or gynaecological stage I–III cancers being planned for curative intent chemotherapy. A total of 270 patients were required for accrual in the study. Exposure(s) Total risk score ranged from 0 (lowest toxicity risk) to 19 (highest toxicity risk). Main outcome(s) and measure(s) The primary endpoint of the study was to evaluate whether the CARG risk score predicted for grade 3–5 toxicities. Results The study cohort of 270 patients had a mean age of 69 (65–83) years, with the most common cancers being gastrointestinal (79%). Fifty-two per cent of patients had atleast one grade 3–5 toxicity. The risk of toxicity was increased with an increasing risk score (42% low risk, 51% medium risk and 79% high risk; p<0.001). There was no association between either Eastern Cooperative Oncology Group (ECOG) performance status (p=0.69) or age-adjusted Charlson Comorbidity Index (p=0.79) risk categories and grade 3–5 chemotherapy toxicities. Conclusions and relevance This study validates the CARG risk score in predicting for grade 3–5 toxicities in geriatric oncology patients receiving curative intent chemotherapy and can be considered as the standard of care before planning chemotherapy in every elderly patient. Trial registration number CTRI/2016/10/007357; Results.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs. METHODS: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization–positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status. RESULTS: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001). CONCLUSION: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).

Importance: The role of olanzapine has not been adequately evaluated in moderately emetogenic chemotherapy (MEC) regimens with or without neurokinin-1 receptor antagonists.Objective: To evaluate whether addition of olanzapine to an MEC regimen reduces nausea, vomiting, and use of nausea rescue medications among patients with solid malignant tumors.Design, Setting, and Participants: This multicenter, open-label phase 3 randomized clinical trial included patients aged 18 years or older with solid malignant tumors who were receiving oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy. The trial was conducted at 3 institutes in India from March 26, 2019, to August 26, 2023; the final cutoff date for analysis was September 10, 2023.Exposure: Patients were randomized 1:1 to dexamethasone, aprepitant, and palonosetron with olanzapine (experimental group) or without olanzapine (observation group). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3 of the chemotherapy regimen.Main Outcomes and Measures: The primary end point was complete response (CR), defined as the proportion of patients with no vomiting, no significant nausea (scored as <5 on a visual analog scale of 1 to 100), and no use of rescue medications for nausea. Secondary end points included the proportion of patients experiencing nausea and chemotherapy-induced nausea and vomiting (CINV), receiving rescue medications, and experiencing adverse events.Results: A total of 560 patients (259 [64%] male; median age, 51 years [range, 19-80 years]) were randomized. The analysis included 544 patients with evaluable data (274 assigned to olanzapine and 270 to observation). Baseline characteristics were evenly matched between the 2 groups. The proportion of patients with CR was significantly greater in the group with (248 [91%]) than without (222 [82%]) olanzapine in the overall 120-hour treatment period (P = .005). Likewise, there were significant differences between the olanzapine and observation groups for nausea control (264 [96%] vs 234 [87%]; P < .001) and CINV (262 [96%] vs 245 [91%]; P = .02) during the overall assessment period, and the proportion of patients receiving rescue medications significantly increased in the observation group (30 [11%]) compared with the olanzapine group (11 [4%]) (P = .001). Grade 1 somnolence was reported by 27 patients (10%) following administration of chemotherapy and olanzapine and by no patients in the observation group.Conclusions and Relevance: In this randomized clinical trial, the addition of olanzapine significantly improved CR rates as well as nausea and vomiting prevention rates in chemotherapy-naive patients who were receiving MEC regimens containing oxaliplatin, carboplatin, or irinotecan. These findings suggest that use of olanzapine should be considered as one of the standards of care in these chemotherapy regimens.Trial Registration: Clinical Trials Registry–India (CTRI) Identifier: CTRI/2018/12/016643

Background: The available evidence in locally advanced rectal cancer (LARC) suggests a low prevalence of deficient mismatch repair (dMMR) protein status, approximating 1–3%. Methods: Patients with LARC who were offered long course chemoradiation (LCRT), as per institution protocol during the period of 1st January 2014 to 31st December 2015 at Tata Memorial Hospital (TMH) in Mumbai were evaluated for outcomes and assessment of MMR status. Results: A total of 419 patients were evaluated for LARC in TMH, of whom 354 were treated with LCRT. Of these 354 patients, 296 were assessable for MMR status based on tissue adequacy for testing. Three patients (1.01%) has dMMR status, while the remaining 293 patients had proficient MMR status. A total of 240 patients (67.8%) underwent curative intent resections. With a median follow-up of 32 months, estimated 3-year recurrence free survival (RFS) and overall survival (OS) for the resected group was 63.5% and 85.2%, respectively, while 3-year event free survival and OS for the unresected cohort was 15.2% and 15.8%, respectively. Signet ring histology, higher ypT stage, involved margin status post resection, and delays (>1 week) in LCRT were associated with inferior OS on multivariate analysis. Conclusions: In a large LARC cohort, a majority of tumors had proficient MMR status, suggesting that MSI as a biomarker may have limited applicability in the management of rectal cancers. Signet ring histology, CRM involvement post resection, higher ypT stage and interruptions in LCRT predicted for inferior OS.