Epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC) is an important subtype of lung cancer. With the existing and ongoing research and multiple targeted therapeutic options available, the treatment landscape of this subset is rapidly evolving. This is the first review article in the series on EGFR-mutant NSCLC in which we describe the structure of EGFR, the molecular biology of common EGFR mutations, diagnostic modalities, and various treatment options for all stages of NSCLC harboring common EGFR mutations. We searched for the articles in various databases including OncoKB, NCBI: PubMed, Embase, Scopus, and MyCancerGenome, using the keywords “EGFR”, “NSCLC”, “Osimertinib”, and “Gefitinib”. To compile this review, a total of 132 articles were utilized.

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) deficiency, an autosomal recessive metabolic disorder, causes a considerable deficit in the patient's metabolism of fluoropyrimidine drugs, most notably 5-fluorouracil (5-FU) and capecitabine. There is a higher frequency of severe toxicities after a fluoropyrimidine regimen among patients with GI and hepatopancreaticobiliary (HPB) malignancies on chemotherapy because of this metabolic deficiency. This prospective study aims to assess the rate of DPD deficiency and clinical significance of DPD deficiency in patients receiving fluoropyrimidine chemotherapy at a tertiary oncology center in India. MATERIALS AND METHODS: From March 2024 to February 2025, we prospectively recruited 146 patients with histologic confirmation of GI and HPB cancers who were commencing a 5-FU– or capecitabine-based regimen. We performed pretreatment DPD tests on all patients using TRUPCR DPYD reverse transcriptase polymerase chain reaction for four known variants. Severe toxicities (Common Terminology Criteria for Adverse Events v5.0) were assessed after the first cycle of chemotherapy. Dose reductions, advances in therapy, and admissions were also noted. RESULTS: Of the 146 study participants, 11 (7.5%) had a DPYD mutation. HapB3 (rs56038477) was the most commonly encountered variant (72.7% of patients), along with registries of DPYD*2A (18.2%) mutation and mutation c.2846A>T (9.1%). Severe toxicities (grade ≥3) were above other grade toxicities (61.6%) in mutation carriers (72.7%) as compared with mutation noncarriers (37.0%, P = .03). Neutropenia, diarrhea, and thrombocytopenia were the common toxicities at a frequency of 18.5%, 12.3%, and 15.1%, respectively. After dose reduction, 90.9% of mutation carriers required a dose reduction versus 14.8% of mutation noncarriers ( P < .001). Both groups had no problems in completing treatment. CONCLUSION: Individuals with DPYD mutations experience increased toxicity and dose adjustments; however, treatment efficacy was not affected. This indicates that a coordinated effort that incorporates routine DPYD testing can mitigate treatment toxicities and individualized fluoropyrimidine dosing for patients with GI and HPB cancers.

Purpose: Gallbladder cancer is highly prevalent in North India and associated with poor survival in advanced disease. Although chemoimmunotherapy improves outcomes in biliary tract cancers, prospective data specific to gallbladder cancer remain limited. We compared gemcitabine-cisplatin (GemCis) with or without durvalumab in patients with advanced gallbladder cancer. Methods: In this ambispective observational cohort study at a North Indian tertiary cancer center (Jan 2023–June 2025), 98 patients with unresectable/metastatic gallbladder cancer received GemCis alone (n=48) or GemCis+durvalumab (n=50) based on drug availability and patient preference after counseling. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: Baseline characteristics were balanced. ORR was 30.0% with durvalumab vs 18.8% with GemCis alone; DCR was 56.0% vs 39.6%. Median PFS was 6.1 vs 4.1 months (HR 0.62, 95% CI 0.45–0.88; P=0.007). Median OS was 14.2 vs 9.7 months (HR 0.69, 95% CI 0.52–0.91; P=0.012). Grade ≥3 adverse events were similar between arms. Immune-related adverse events occurred in 20% receiving durvalumab (grade ≥3: 2%), all manageable. Conclusions: In this gallbladder cancer-specific cohort, durvalumab added to GemCis was associated with improved PFS and OS without increased toxicity. These findings support further evaluation of chemoimmunotherapy for advanced gallbladder cancer in high-incidence regions.

Purpose: Gallbladder cancer is an aggressive malignancy with poor outcomes in advanced disease. Evidence specific to gallbladder cancer from routine clinical practice remains limited. We compared outcomes among patients treated with gemcitabine–cisplatin (GemCis) with or without durvalumab. Methods: This single-centre ambispective observational cohort included 98 patients with unresectable, recurrent, or metastatic gallbladder cancer treated from January 2023 through June 2025. Forty-eight received GemCis alone and 50 received GemCis plus durvalumab; treatment selection was based on drug availability and patient preference after counselling. Follow-up continued through December 2025. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: Median PFS was 6.1 months with GemCis plus durvalumab and 4.1 months with GemCis alone (unadjusted HR 0.55, 95% CI 0.36–0.85; p = 0.007). Median OS was 14.2 and 9.7 months, respectively (unadjusted HR 0.58, 95% CI 0.35–0.99; p = 0.041). In 6-month landmark analyses, the PFS difference persisted (HR 0.39, 95% CI 0.19–0.81) but the OS difference did not (HR 1.15, 95% CI 0.61–2.17). In multivariable Cox models, the adjusted HR was 0.55 (95% CI 0.35–0.85) for PFS and 0.58 (95% CI 0.34–0.98) for OS. Objective response rates were 30.0% (15/50) and 18.8% (9/48), and disease control rates were 56.0% (28/50) and 39.6% (19/48), respectively. The response-rate differences were not statistically significant (Fisher’s exact p = 0.243 and p = 0.112, respectively). Immune-related adverse events were reported in 20% of patients receiving durvalumab, including grade ≥3 events in 2%. Conclusion: In this nonrandomized cohort, durvalumab-containing treatment was associated with numerically longer PFS and OS, but the OS difference was not maintained in landmark analysis. Residual confounding, adjustment limited to measured baseline factors, possible bias related to maintenance exposure, and unavailable systematic biomarker and subsequent-treatment data limit causal interpretation. The findings are hypothesis-generating.